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Sökning: WFRF:(Evander Magnus)

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1.
  • Ecke, Frauke, et al. (författare)
  • Orthohantaviruses in the Arctic : present and future
  • 2022
  • Ingår i: Arctic one health. - Cham : Springer. - 9783030878528 - 9783030878559 - 9783030878535 ; , s. 393-414
  • Bokkapitel (refereegranskat)abstract
    • Orthohantaviruses, family Hantaviridae, are globally distributed except for Antarctica where they are absent. In animals, orthohantaviruses are transmitted horizontally, either directly through aggressive interactions and grooming or by inhaling infectious particles shed from urine, feces, or saliva in the environment. Humans become infected by inhaling aerosols of the virus-contaminated excretions of small mammals. Orthohantaviral infections in humans cause severe hantavirus pulmonary syndrome (HPS) in the North American Artic and hemorrhagic fever with renal syndrome (HFRS) in the Eurasian Arctic. In the Arctic, 16 rodent species (order Rodentia) and five shrew species (order Eulipotyphla) have been identified as reservoirs of orthohantaviruses by RNA detection. The two most important reservoir rodents in the Arctic are the bank vole (Myodes glareolus) in Eurasia carrying Puumala orthohantavirus (PUUV) and North American deermouse (Peromyscus maniculatus) in the North American Arctic carrying Sin Nombre orthohantavirus (SNV); both rodents being habitat generalists occurring in natural and human-modified habitats. Global warming, either independently or in combination with onshore exploitation of natural resources, is expected to increase the distribution range of reservoirs (including bank vole and North American deermouse, rats (Rattus rattus and R. norvegicus), house mouse (Mus musculus) and field mice (Apodemus spp.)), and their associated orthohantaviruses. These changes pose the risk of introducing New World orthohantaviruses (e.g., Jemez Springs virus (JMSV) and SNV) to areas where so far only Old World orthohantaviruses (e.g., Hantaan orthohantavirus (HTNV) and PUUV) occur and vice versa. Climate change in the Arctic will likely also promote transmission and prevalence of orthohantaviruses in their reservoirs and hence increase zoonotic risk. The expected environmental changes call for increased surveillance and preparedness to mitigate potential outbreaks of orthohantavirus diseases in humans.
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2.
  • Ecke, Frauke, et al. (författare)
  • Puumala Orthohantavirus Infection Does Not Affect the Trapping Success of Its Reservoir Host
  • 2022
  • Ingår i: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert. - 1530-3667 .- 1557-7759. ; 22:5, s. 297-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Pathogens might affect behavior of infected reservoir hosts and hence their trappability, which could bias population estimates of pathogen prevalence. In this study, we used snap-trapping data on Puumala orthohantavirus (PUUV)-infected (n = 1619) and noninfected (n = 6940) bank voles (Myodes glareolus) from five vole cycles, normally representing increase, peak, and decline phase, to evaluate if infection status affected trapping success. If PUUV infection, as previously suggested, increases activity and/or mobility, we would expect a higher proportion of infected than noninfected specimens in the first trapping night. However, the proportion of PUUV-infected voles did not differ across the three trapping nights. We conclude that PUUV infection did not affect trapping success, confirming snap trapping as an appropriate trapping method for studies on PUUV prevalence and likely other orthohantaviruses.
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3.
  • Khalil, Hussein, et al. (författare)
  • Declining ecosystem health and the dilution effect
  • 2016
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • The "dilution effect" implies that where species vary in susceptibility to infection by a pathogen, higher diversity often leads to lower infection prevalence in hosts. For directly transmitted pathogens, non-host species may "dilute" infection directly (1) and indirectly (2). Competitors and predators may (1) alter host behavior to reduce pathogen transmission or (2) reduce host density. In a well-studied system, we tested the dilution of the zoonotic Puumala hantavirus (PUUV) in bank voles (Myodes glareolus) by two competitors and a predator. Our study was based on long-term PUUV infection data (2003-2013) in northern Sweden. The field vole (Microtus agrestis) and the common shrew (Sorex araneus) are bank vole competitors and Tengmalm's owl (Aegolius funereus) is a main predator of bank voles. Infection probability in bank voles decreased when common shrew density increased, suggesting that common shrews reduced PUUV transmission. Field voles suppressed bank vole density in meadows and clear-cuts and indirectly diluted PUUV infection. Further, Tengmalm's owl decline in 1980-2013 may have contributed to higher PUUV infection rates in bank voles in 2003-2013 compared to 1979-1986. Our study provides further evidence for dilution effect and suggests that owls may have an important role in reducing disease risk.
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4.
  • Khalil, Hussein, et al. (författare)
  • Dynamics and Drivers of Hantavirus Prevalence in Rodent Populations
  • 2014
  • Ingår i: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert, Inc. publishers. - 1530-3667 .- 1557-7759. ; 14:8, s. 537-551
  • Forskningsöversikt (refereegranskat)abstract
    • Human encroachment on wildlife habitats has contributed to the emergence of several zoonoses. Pathogenic hantaviruses are hosted by rodents and cause severe diseases in the Americas and Eurasia. We reviewed several factors that potentially drive prevalence (the proportion of infected rodents) in host populations. These include demography, behavior, host density, small mammal diversity, predation, and habitat and landscape characteristics. This review is the first to include a quantitative summary of the literature investigating hantavirus prevalence in rodents. Demographic structure and density were investigated the most and predation the least. Reported effects of demographic structure and small mammal diversity were consistent, whereby reproductive males were most likely to be infected and prevalence decreased with small mammal diversity. The influences of habitat and landscape properties are often complex and indirect. The relationship between density and prevalence merits more investigation. Most hantavirus hosts are habitat generalists and their control is challenging. Incorporating all potential factors and their interactions is essential to understanding and controlling infection in host populations.
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5.
  • Khalil, Hussein, et al. (författare)
  • Spatial prediction and validation of zoonotic hazard through micro-habitat properties : where does Puumala hantavirus hole - up?
  • 2017
  • Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To predict the risk of infectious diseases originating in wildlife, it is important to identify habitats that allow the co-occurrence of pathogens and their hosts. Puumala hantavirus (PUUV) is a directly-transmitted RNA virus that causes hemorrhagic fever in humans, and is carried and transmitted by the bank vole (Myodes glareolus). In northern Sweden, bank voles undergo 3-4 year population cycles, during which their spatial distribution varies greatly.Methods: We used boosted regression trees; a technique inspired by machine learning, on a 10 - year time-series (fall 2003-2013) to develop a spatial predictive model assessing seasonal PUUV hazard using micro-habitat variables in a landscape heavily modified by forestry. We validated the models in an independent study area approx. 200 km away by predicting seasonal presence of infected bank voles in a five-year-period (2007-2010 and 2015).Results: The distribution of PUUV-infected voles varied seasonally and inter-annually. In spring, micro-habitat variables related to cover and food availability in forests predicted both bank vole and infected bank vole presence. In fall, the presence of PUUV-infected voles was generally restricted to spruce forests where cover was abundant, despite the broad landscape distribution of bank voles in general. We hypothesize that the discrepancy in distribution between infected and uninfected hosts in fall, was related to higher survival of PUUV and/ or PUUV-infected voles in the environment, especially where cover is plentiful.Conclusions: Moist and mesic old spruce forests, with abundant cover such as large holes and bilberry shrubs, also providing food, were most likely to harbor infected bank voles. The models developed using long-term and spatially extensive data can be extrapolated to other areas in northern Fennoscandia. To predict the hazard of directly transmitted zoonoses in areas with unknown risk status, models based on micro-habitat variables and developed through machine learning techniques in well-studied systems, could be used.
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6.
  • Khalil, Hussein, et al. (författare)
  • The importance of bank vole density and rainy winters in predicting nephropathia epidemica incidence in Northern Sweden.
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Pathogenic hantaviruses (family Bunyaviridae, genus Hantavirus) are rodent-borne viruses causing hemorrhagic fever with renal syndrome (HFRS) in Eurasia. In Europe, there are more than 10,000 yearly cases of nephropathia epidemica (NE), a mild form of HFRS caused by Puumala virus (PUUV). The common and widely distributed bank vole (Myodes glareolus) is the host of PUUV. In this study, we aim to explain and predict NE incidence in boreal Sweden using bank vole densities. We tested whether the number of rainy days in winter contributed to variation in NE incidence. We forecast NE incidence in July 2013-June 2014 using projected autumn vole density, and then considering two climatic scenarios: 1) rain-free winter and 2) winter with many rainy days. Autumn vole density was a strong explanatory variable of NE incidence in boreal Sweden in 1990-2012 (R2 = 79%, p<0.001). Adding the number of rainy winter days improved the model (R2 = 84%, p<0.05). We report for the first time that risk of NE is higher in winters with many rainy days. Rain on snow and ground icing may block vole access to subnivean space. Seeking refuge from adverse conditions and shelter from predators, voles may infest buildings, increasing infection risk. In a rainy winter scenario, we predicted 812 NE cases in boreal Sweden, triple the number of cases predicted in a rain-free winter in 2013/2014. Our model enables identification of high risk years when preparedness in the public health sector is crucial, as a rainy winter would accentuate risk.
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7.
  • Magnusson, Magnus, et al. (författare)
  • Spatial and temporal variation of hantavirus bank vole infection in managed forest landscapes
  • 2015
  • Ingår i: Ecosphere. - 2150-8925 .- 2150-8925. ; 6:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Zoonoses are major contributors to emerging infectious diseases globally. Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis caused by rodent-borne hantaviruses. In Europe, Puumala hantavirus (PUUV) carried and shed by the bank vole (Myodes glareolus), is the most common cause of HFRS. We explore the relationship of PUUV infection in bank voles, as measured by PUUV antibody detection, with habitat and landscape scale properties during two successive vole cycles in boreal Sweden. Our analysis revealed that PUUV infection in the population was not uniform between cycles and across different landscapes. The mean density index of PUUV antibody positive and negative bank voles were highest in old forest, second highest in cut-over forest (approx. 0-30 years old) and lowest on mires. Most importantly, old forest was the core habitat, where PUUV antibody positive bank voles were found through the low density phase and the transition between successive vole cycles. In spring, occurrence of antibody positive voles was negatively related to the proportion of cut-over forest in the surrounding landscape, suggesting that large scale human induced land-use change altered the occurrence of PUUV infection in voles which has not been shown before. Dependence of PUUV infection on habitat and landscape structure, and the variation in infection load within and between cycles are of importance for human risk assessment.
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8.
  • Sipari, Saana, et al. (författare)
  • Climate change accelerates winter transmission of a zoonotic pathogen
  • 2022
  • Ingår i: Ambio. - : Springer. - 0044-7447 .- 1654-7209. ; 51:3, s. 508-517
  • Tidskriftsartikel (refereegranskat)abstract
    • Many zoonotic diseases are weather sensitive, raising concern how their distribution and outbreaks will be affected by climate change. At northern high latitudes, the effect of global warming on especially winter conditions is strong. By using long term monitoring data (1980–1986 and 2003–2013) from Northern Europe on temperature, precipitation, an endemic zoonotic pathogen (Puumala orthohantavirus, PUUV) and its reservoir host (the bank vole, Myodes glareolus), we show that early winters have become increasingly wet, with a knock-on effect on pathogen transmission in its reservoir host population. Further, our study is the first to show a climate change effect on an endemic northern zoonosis, that is not induced by increased host abundance or distribution, demonstrating that climate change can also alter transmission intensity within host populations. Our results suggest that rainy early winters accelerate PUUV transmission in bank voles in winter, likely increasing the human zoonotic risk in the North.
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9.
  • Abdelrahim, Nada A., et al. (författare)
  • Human herpes virus type-6 is associated with central nervous system infections in children in Sudan
  • 2022
  • Ingår i: African Journal of Laboratory Medicine. - : AOSIS. - 2225-2002 .- 2225-2010. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Human herpes virus type-6 (HHV-6) is increasingly recognised as a febrile agent in children. However, less is known in sub-Saharan African countries, including Sudan.Objective: We investigated the involvement of HHV-6 in paediatric central nervous system (CNS) infections in Khartoum, Sudan.Methods: Febrile patients aged up to 15 years with suspected CNS infections at Omdurman Hospital for Children from 01 December 2009 to 01 August 2010 were included. Viral DNA was extracted from leftover cerebrospinal fluid (CSF) specimens and quantitatively amplified by real-time polymerase chain reaction (PCR) at Umeå University in Sweden.Results: Of 503 CSF specimens, 13 (2.6%) were positive for HHV-6 (33.0% [13/40 of cases with proven infectious meningitis]). The median thermal cycle threshold for all HHV-6-positive specimens was 38 (range: 31.9-40.8). The median number of virus copies was 281.3/PCR run (1 × 105 copies/mL CSF; range: 30-44 × 103 copies/PCR run [12 × 103 - 18 × 106 copies/mL CSF]). All positive patients presented with fever and vomiting; 86.0% had seizures. The male-to-female ratio was 1:1; 50.0% were toddlers, 42.0% infants and 8.0% teenagers. Most (83.0%) were admitted in the dry season and 17.0% in the rainy season. Cerebrospinal fluid leukocytosis was seen in 33.0%, CSF glucose levels were normal in 86.0% and low in 14.0%, and CSF protein levels were low in 14.0% and high in 43.0%.Conclusion: Among children in Sudan with CNS infections, HHV-6 is common. Studies on the existence and spread of HHV-6 chromosomal integration in this population are needed.
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10.
  • Abdelrahim, Nada Abdelghani, et al. (författare)
  • Viral meningitis in Sudanese children : differentiation, etiology and review of literature
  • 2022
  • Ingår i: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 101:46
  • Forskningsöversikt (refereegranskat)abstract
    • Diagnosis of viral meningitis (VM) is uncommon practice in Sudan and there is no local viral etiological map. We therefore intended to differentiate VM using standardized clinical codes and determine the involvement of herpes simplex virus types-1 and 2 (HSV-1/2), varicella zoster virus, non-polio human enteroviruses (HEVs), and human parechoviruses in meningeal infections in children in Sudan. This is a cross-sectional hospital-based study. Viral meningitis was differentiated in 503 suspected febrile attendee of Omdurman Hospital for Children following the criteria listed in the Clinical Case Definition for Aseptic/Viral Meningitis. Patients were children age 0 to 15 years. Viral nucleic acids (DNA/RNA) were extracted from cerebrospinal fluid (CSF) specimens using QIAamp® UltraSens Virus Technology. Complementary DNA was prepared from viral RNA using GoScriptTM Reverse Transcription System. Viral nucleic acids were amplified and detected using quantitative TaqMan® Real-Time and conventional polymerase chain reactions (PCRs). Hospital diagnosis of VM was assigned to 0%, when clinical codes were applied; we considered 3.2% as having VM among the total study population and as 40% among those with proven infectious meningitis. Two (0.4%) out of total 503 CSF specimens were positive for HSV-1; Ct values were 37.05 and 39.10 and virus copies were 652/PCR run (261 × 103/mL CSF) and 123/PCR run (49.3 × 103/mL CSF), respectively. Other 2 (0.4%) CSF specimens were positive for non-polio HEVs; Ct values were 37.70 and 38.30, and the approximate virus copies were 5E2/PCR run (~2E5/mL CSF) and 2E2/PCR run (~8E4/mL CSF), respectively. No genetic materials were detected for HSV-2, varicella zoster virus, and human parechoviruses. The diagnosis of VM was never assigned by the hospital despite fulfilling the clinical case definition. Virus detection rate was 10% among cases with proven infectious meningitis. Detected viruses were HSV-1 and non-polio HEVs. Positive virus PCRs in CSFs with normal cellular counts were seen.
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11.
  • Affognon, Hippolyte, et al. (författare)
  • Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya
  • 2017
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.
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12.
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13.
  • Ahlm, Clas, et al. (författare)
  • Seroprevalence of Sindbis virus and associated risk factors in northern Sweden
  • 2014
  • Ingår i: Epidemiology and Infection. - : Cambridge University Press. - 0950-2688 .- 1469-4409. ; 142:7, s. 1559-1565
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever and arthritis which often leads to long-lasting arthralgia. To determine the seroprevalence of SINV and associated risk factors in northern Sweden, a randomly selected population aged between 25 and 74 years were invited to join the MONICA study. Serum from 1611 samples were analysed for specific IgG antibodies. Overall, 2·9% had IgG against SINV. More men (3·7%) than women (2·0%) were SINV seropositive (P = 0·047) and it was more common in subjects with a lower educational level (P = 0·013) and living in small, rural communities (P < 0·001). Seropositivity was associated with higher waist circumference (P = 0·1), elevated diastolic blood pressure (P = 0·037), and history of a previous stroke (P = 0·011). In a multiple logistic regression analysis, adjusting for known risk factors for stroke, seropositivity for SINV was an independent predictor of having had a stroke (odds ratio 4·3, 95% confidence interval 1·4–13·0,P = 0·011).
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14.
  • Ahmed Hassan Ahmed, Osama, 1972- (författare)
  • Rift Valley fever : challenges and new insights for prevention and control using the “One Health” approach
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rift Valley fever (RVF) is an emerging viral zoonosis that causes frequent outbreaks in east Africa and on the Arabian Peninsula. The likelihood of RVF global expansion due to climate change and human anthropogenic factors is an important issue. The causative agent, RVF virus, is an arbovirus that is transmitted by several mosquito species and is able to infect a wide range of livestock as well as people. The infection leads to mass abortions and death in livestock and a potentially deadly hemorrhagic fever in humans. RVF has severe socio-economic consequences such as animal trade bans between countries, disruption of food security, and economic disaster for farmers and pastoralists as well as for countries. Human behavior such as direct contact with infected animals or their fluids and exposure to mosquito bites increases the risk for contracting the disease.To better understand the challenges associated with RVF outbreaks and to explore prevention and control strategies, we used the One Health approach. The local community had to be involved to understand the interaction between the environment, animals, and humans. We focused on Sudan, Saudi Arabia, and Kenya. First, we systematically reviewed the literature and then we performed cross sectional community-based studies using a special One Health questionnaire. Climatic and remote sensing data were used in combination with statistics to develop a sub-region predictive model for RVF.For both Saudi Arabia and Sudan, the ecology and environment of the affected areas were similar. These areas included irrigation canals and excessive rains that provide an attractive habitat for mosquito vectors to multiply. The surveillance systems were unable to detect the virus in livestock before it spread to humans. Ideally, livestock should serve as sentinels to prevent loss of human lives, but the situation here was reversed. Differences between countries regarding further spread of RVF was mainly determined by better economic and infrastructure resources.In Sudan, there was a lack of knowledge and appropriate practices at the studied community regarding RVF disease symptoms and risk factors for both animals and humans. The community was hesitant in notifying the authorities about RVF suspicion in livestock due to the lack of a compensation system. The perceived role of the community in controlling RVF was fragmented, increasing the probability of RVF transmission and disease.In Kenya, our study found that better knowledge about RVF does not always translate to more appropriate practices that avoid exposure to the disease. However, the combination of good knowledge, attitudes, and practices may explain why certain communities were less affected. Strategies to combat RVF should consider socio-cultural and behavioral differences among communities. We also noticed that RVF outbreaks in Kenya occurred in regions with high livestock density exposed to heavy rains and wet soil fluxes, which could be measured by evapotranspiration and vegetation seasonality variables. We developed a RVF risk map on a sub-regional scale. Future outbreaks could be better managed if such relevant RVF variables are integrated into early warning systems.To confront RVF outbreaks, a policy is needed that better incorporates ecological factors and human interactions with livestock and environment that help the RVF pathogen spread. Early detection and notification of RVF is essential because a delay will threaten the core of International Health Regulations (IHR), which emphasizes the share of information during a transboundary disease outbreak to avoid unnecessary geographical expansion.
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15.
  • Andersen, Petter I., et al. (författare)
  • Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine
  • 2019
  • Ingår i: Viruses. - : MDPI. - 1999-4915. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.
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16.
  • Baudin, Maria, 1982-, et al. (författare)
  • Association of Rift Valley fever virus infection with miscarriage in Sudanese women : a cross-sectional study
  • 2016
  • Ingår i: The Lancet Global Health. - 2214-109X. ; 4:11, s. e864-e871
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Rift Valley fever virus is an emerging mosquito-borne virus that causes infections in animals and human beings in Africa and the Arabian Peninsula. Outbreaks of Rift Valley fever lead to mass abortions in livestock, but such abortions have not been identified in human bezings. Our aim was to investigate the cause of miscarriages in febrile pregnant women in an area endemic for Rift Valley fever.METHODS: Pregnant women with fever of unknown origin who attended the governmental hospital of Port Sudan, Sudan, between June 30, 2011, and Nov 17, 2012, were sampled at admission and included in this cross-sectional study. Medical records were retrieved and haematological tests were done on patient samples. Presence of viral RNA as well as antibodies against a variety of viruses were analysed. Any association of viral infections, symptoms, and laboratory parameters to pregnancy outcome was investigated using Pearson's χ(2) test.FINDINGS: Of 130 pregnant women with febrile disease, 28 were infected with Rift Valley fever virus and 31 with chikungunya virus, with typical clinical and laboratory findings for the infection in question. 15 (54%) of 28 women with an acute Rift Valley fever virus infection had miscarriages compared with 12 (12%) of 102 women negative for Rift Valley fever virus (p<0·0001). In a multiple logistic regression analysis, adjusting for age, haemorrhagic disease, and chikungunya virus infection, an acute Rift Valley fever virus infection was an independent predictor of having a miscarriage (odds ratio 7·4, 95% CI 2·7-20·1; p<0·0001).INTERPRETATION: This study is the first to show an association between infection with Rift Valley fever virus and miscarriage in pregnant women. Further studies are warranted to investigate the possible mechanisms. Our findings have implications for implementation of preventive measures, and evidence-based information to the public in endemic countries should be strongly recommended during Rift Valley fever outbreaks.FUNDING: Schlumberger Faculty for the Future, CRDF Global (31141), the Swedish International Development Cooperation Agency, the County Council of Västerbotten, and the Faculty of Medicine, Umeå University.
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17.
  • Baudin, Maria, 1982-, et al. (författare)
  • Importance of charge interactions in Rift Valley fever virus attachment to host cells
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • The mosquito-borne Rift Valley fever virus (RVFV) cause disease in both humans and animals and can infect a large range of animals as well as humans. Many different cell types are infected both in vivo and in vitro. To enter a cell the virus needs to attach and enter, and this initial binding to the host cell surface could depend on both general mechanisms, and different specific receptors. Our aim was to characterize determinants for RVFV entry into its host cells.To examine RVFV attachment to host cells we based our experimental assay on RVF virus-like particles containing a reporter gene. The enveloped RVFV uses protruding glycoproteins (Gn and Gc) for attachment and entry and to investigate potential virus-cell surface interactions, the net surface charge of the glycoproteins was first calculated. The RVFV glycoprotein Gn had a predicted isoelectric point (pI) of 7.6 and a net positive charge of +6.9 at pH 7.0, suggesting a charge interaction between the Gn ectodomain and the negatively charged cell surface. RVFV Gc on the other hand, was highly negatively charged, -12.8 at neutral pH, most probably reflecting that Gc is not exposed until after receptor binding. To characterize the general conditions needed for RVFV attachment, cells or virus were treated with various compounds. Both sodium chloride and the negatively charged heparin inhibited RVF virus-like particle infection, strongly indicating that viral binding was charge-dependent. Treatment with sodium periodate pointed to a carbohydrate structure as a cellular interaction partner. Removal of sialic acid or heparan sulfate receptors on the cell surface by enzymatic treatment and blocking of the heparan sulfate receptor did not inhibit virus attachment.In conclusion, RVFV binding to host cells was charge dependent and the results point to a carbohydrate structure with negative charge as a potential attachment factor.
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18.
  • Baudin, Maria, 1982- (författare)
  • Rift Valley fever : consequences of virus-host interactions
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rift Valley fever virus (RVFV) is a mosquito-borne virus which has the ability to infect a large variety of animals including humans in Africa and Arabian Peninsula. The abortion rate among these animals are close to 100%, and young animals develop severe disease which often are lethal.In humans, Rift Valley fever (RVF) presents in most cases as a mild illness with influenza-like symptoms. However, in about 8% of the cases it progresses into a more severe disease with a high case fatality rate. Since there is such a high abortion rate among infected animals, a link between human miscarriage and RVFV has been suggested, but never proven.We could in paper I for the first time show an association between acute RVFV infection and miscarriage in humans. We observed an increase in pregnant women arriving at the Port Sudan Hospital with fever of unknown origin, and several of the patients experienced miscarriage. When we analysed their blood samples for several viral diseases we found that many had an acute RVFV infection and of these, 54% experienced a miscarriage. The odds of having a miscarriage was 7 times higher for RVFV patients compared to the RVFV negative women of which only 12% miscarried. These results indicated that RVFV infection could be a contributing factor to miscarriage.RVFV is an enveloped virus containing the viral glycoproteins n and c (Gn and Gc respectively), where Gn most likely is responsible for the initial cellular contact. The protein DC-SIGN on dendritic cells and the glycosaminoglycan heparan sulfate has been suggested as cellular receptors for RVFV, however other mechanisms are probably also involved in binding and entry. Charge is a driving force for molecular interaction and has been shown to be important for cellular attachment of several viruses, and in paper II we could show that when the charge around the cells was altered, the infection was affected. We also showed that Gn most likely has a positive charge at a physiological pH.When we added negatively charged molecules to the viral particles before infection, we observed a decreased infection efficiency, which we also observed after removal of carbohydrate structures from the cell surface.Our results suggested that the cellular interaction partner for initial attachment is a negatively charged carbohydrate. Further investigations into the mechanisms of RVFV cellular interactions has to be undertaken in order to understand, and ultimately prevent, infection and disease.There is currently no vaccine approved for human use and no specific treatments for RVF, so there is a great need for developing safe effective drugs targeting this virus. We designed a whole-cell based high-throughput screen (HTS) assay which we used to screen libraries of small molecular compounds for anti-RVFV properties. After dose-response and toxicity analysis of the initial hits, we identified six safe and effective inhibitors of RVFV infection that with further testing could become drug candidates for treatment of RVF. This study demonstrated the application of HTS using a whole-cell virus replication reporter gene assay as an effective method to identify novel compounds with potential antiviral activity against RVFV.
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19.
  • Bergqvist, Joakim, et al. (författare)
  • Detection and Isolation of Sindbis Virus from Mosquitoes Captured During an Outbreak in Sweden, 2013
  • 2015
  • Ingår i: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert Inc. - 1530-3667 .- 1557-7759. ; 15:2, s. 133-140
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosquito-borne alphaviruses have the potential to cause large outbreaks throughout the world. Here we investigated the causative agent of an unexpected Sindbis virus (SINV) outbreak during August-September, 2013, in a previously nonendemic region of Sweden. Mosquitoes were collected using carbon dioxide-baited CDC traps at locations close to human cases. The mosquitoes were initially screened as large pools by SINV-specific quantitative RT-PCR, and the SINV-positive mosquitoes were species determined by single-nucleotide polymorphism (SNP) analysis, followed by sequencing the barcoding region of the cytochrome oxidase I gene. The proportion of the collected mosquitoes was determined by a metabarcoding strategy. By using novel strategies for PCR screening and genetic typing, a new SINV strain, Lovanger, was isolated from a pool of 1600 mosquitoes composed of Culex, Culiseta, and Aedes mosquitoes as determined by metabarcoding. The SINV-positive mosquito Culiseta morsitans was identified by SNP analysis and sequencing. After whole-genome sequencing and phylogenetic analysis, the SINV Lovanger isolate was shown to be most closely similar to recent Finnish SINV isolates. In conclusion, within a few weeks, we were able to detect and isolate a novel SINV strain and identify the mosquito vector during a sudden SINV outbreak.
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20.
  • Bergstedt Oscarsson, Kristina, et al. (författare)
  • Human Puumala hantavirus infection in northern Sweden : increased seroprevalence and association to risk and health factors
  • 2016
  • Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The rodent borne Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome in central and northern Europe. The number of cases has increased and northern Sweden has experienced large outbreaks in 1998 and 2006-2007 which raised questions regarding the level of immunity in the human population.METHODS: A randomly selected population aged between 25 and 74 years from northern Sweden were invited during 2009 to participate in a WHO project for monitoring of trends and determinants in cardiovascular disease. Health and risk factors were evaluated and sera from 1,600 participants were available for analysis for specific PUUV IgG antibodies using a recombinant PUUV nucleocapsid protein ELISA.RESULTS: The overall seroprevalence in the investigated population was 13.4 %, which is a 50 % increase compared to a similar study only two decades previously. The prevalence of PUUV IgG increased with age, and among 65-75 years it was 22 %. More men (15.3 %) than women (11.4 %) were seropositive (p < 0.05). The identified risk factors were smoking (OR = 1.67), living in rural areas (OR = 1.92), and owning farmland or forest (OR = 2.44). No associations were found between previous PUUV exposure and chronic lung disease, diabetes, hypertension, renal dysfunction, stroke or myocardial infarction.CONCLUSIONS: PUUV is a common infection in northern Sweden and there is a high life time risk to acquire PUUV infection in endemic areas. Certain risk factors as living in rural areas and smoking were identified. Groups with increased risk should be targeted for future vaccination when available, and should also be informed about appropriate protection from rodent secreta.
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21.
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22.
  • Björkström, Niklas K, et al. (författare)
  • Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus
  • 2011
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 208:1, s. 13-21
  • Tidskriftsartikel (refereegranskat)abstract
    • Natural killer (NK) cells are known to mount a rapid response to several virus infections. In experimental models of acute viral infection, this response has been characterized by prompt NK cell activation and expansion followed by rapid contraction. In contrast to experimental model systems, much less is known about NK cell responses to acute viral infections in humans. We demonstrate that NK cells can rapidly expand and persist at highly elevated levels for >60 d after human hantavirus infection. A large part of the expanding NK cells expressed the activating receptor NKG2C and were functional in terms of expressing a licensing inhibitory killer cell immunoglobulin-like receptor (KIR) and ability to respond to target cell stimulation. These results demonstrate that NK cells can expand and remain elevated in numbers for a prolonged period of time in humans after a virus infection. In time, this response extends far beyond what is considered normal for an innate immune response.
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23.
  • Drobni, Peter, et al. (författare)
  • Carboxy-fluorescein diacetate, succinimidyl ester labeled papillomavirus virus-like particles fluoresce after internalization and interact with heparan sulfate for binding and entry
  • 2003
  • Ingår i: Virology. - 0042-6822 .- 1096-0341. ; 310:1, s. 163-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Human papillomaviruses (HPVs) infect epithelial cells and are associated with genital carcinoma. Most epithelial cell lines express cell-surface glycosaminoglycans (GAGs) usually found attached to the protein core of proteoglycans. Our aim was to study how GAGs influenced HPV entry. Using a human keratinocyte cell line (HaCaT), preincubation of HPV virus-like particles (VLPs) with GAGs showed a dose-dependent inhibition of binding. The IC(50) (50% inhibition) was only 0.5 microg/ml for heparin, 1 microg/ml for dextran sulfate, and 5-10 microg/ml for heparan sulfate from mucosal origin. Mutated chinese hamster ovary (CHO) cell lines lacking heparan sulfate or all GAGs were unable to bind HPV VLPs. Here we also report a method to study internalization by using VLPs labeled with carboxy-fluorescein diacetate, succinimidyl ester, a fluorochrome that is only activated after cell entry. Pretreatment of labeled HPV VLPs with heparin inhibited uptake, suggesting a primary interaction between HPV and cell-surface heparan sulfate.
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24.
  • Drobni, Peter, et al. (författare)
  • Lactoferrin inhibits human papillomavirus binding and uptake in vitro.
  • 2004
  • Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 64:1, s. 63-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Lactoferrin (LF), a member of the transferrin family, is a bi-globular protein secreted in milk, saliva, tears, seminal fluid, endocervix and vaginal secretions. LF is an important player in the defence against pathogenic microorganisms and has also been shown to have activity against several viruses including herpesvirus, adenovirus, rotavirus and poliovirus. The antiviral activity of LF is directed against the early steps of viral infection and the LF antiviral effect against herpesvirus is mediated through LF binding to the herpesvirus receptor heparan sulfate. Human papillomavirus (HPV) causes genital warts and is a prerequisite for cervical cancer. HPV can also use heparan sulfate on the cell surface as a receptor. We studied the inhibition by LF on HPV entry by incubating HaCaT cells and HPV-16 virus-like particles (VLPs) with either human (HLF) or bovine lactoferrin (BLF). LF inhibited internalization of HPV-16 particles using CFDA-SE-labelled VLPs that only fluoresce after internalisation. By using a western blot assay we also found dose-dependent LF inhibition of HPV-16 VLP binding to the HaCaT cell surface. BLF was a more potent inhibitor of HPV entry than human LF. It was also clear that LF acted early in the HPV uptake process.
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25.
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26.
  • Ecke, Frauke, et al. (författare)
  • Wildfire-induced short-term changes in a small mammal community increase prevalence of a zoonotic pathogen?
  • 2019
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9:22, s. 12459-12470
  • Tidskriftsartikel (refereegranskat)abstract
    • Natural disturbances like droughts and fires are important determinants of wildlife community structure and are suggested to have important implications for prevalence of wildlife-borne pathogens. After a major wildfire affecting >1,600 ha of boreal forest in Sweden in 2006, we took the rare opportunity to study the short-term response (2007-2010 and 2015) of small mammal community structure, population dynamics, and prevalence of the Puumala orthohantavirus (PUUV) hosted by bank voles (Myodes glareolus). We performed snap-trapping in permanent trapping plots in clear-cuts (n = 3), unburnt reference forests (n = 7), and the fire area (n = 7) and surveyed vegetation and habitat structure. Small mammal species richness was low in all habitats (at maximum three species per trapping session), and the bank vole was the only small mammal species encountered in the fire area after the first postfire year. In autumns of years of peak rodent densities, the trapping index of bank voles was lowest in the fire area, and in two of three peak-density years, it was highest in clear-cuts. Age structure of bank voles varied among forest types with dominance of overwintered breeders in the fire area in the first postfire spring. PUUV infection probability in bank voles was positively related to vole age. Infection probability was highest in the fire area due to low habitat complexity in burnt forests, which possibly increased encounter rate among bank voles. Our results suggest that forest fires induce cascading effects, including fast recovery/recolonization of fire areas by generalists like bank voles, impoverished species richness of small mammals, and altered prevalence of a rodent-borne zoonotic pathogen. Our pilot study suggests high human infection risk upon encountering a bank vole in the fire area, however, with even higher overall risk in unburnt forests due to their higher vole numbers.
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27.
  • Engdahl, Cecilia, et al. (författare)
  • Identification of Swedish mosquitoes based on molecular barcoding of the COI gene and SNP analysis
  • 2014
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 14:3, s. 478-488
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosquito-borne infectious diseases are emerging in many regions of the world. Consequently, surveillance of mosquitoes and concomitant infectious agents is of great importance for prediction and prevention of mosquito-borne infectious diseases. Currently, morphological identification of mosquitoes is the traditional procedure. However, sequencing of specified genes or standard genomic regions, DNA barcoding, has recently been suggested as a global standard for identification and classification of many different species. Our aim was to develop a genetic method to identify mosquitoes and to study their relationship. Mosquitoes were captured at collection sites in northern Sweden and identified morphologically before the cytochrome c oxidase subunit I (COI) gene sequences of 14 of the most common mosquito species were determined. The sequences obtained were then used for phylogenetic placement, for validation and benchmarking of phenetic classifications and finally to develop a hierarchical PCR-based typing scheme based on single nucleotide polymorphism sites (SNPs) to enable rapid genetic identification, circumventing the need for morphological characterization. The results showed that exact phylogenetic relationships between mosquito taxa were preserved at shorter evolutionary distances, but at deeper levels, they could not be inferred with confidence using COI gene sequence data alone. Fourteen of the most common mosquito species in Sweden were identified by the SNP/PCR-based typing scheme, demonstrating that genetic typing using SNPs of the COI gene is a useful method for identification of mosquitoes with potential for worldwide application.
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28.
  • Evander, Mikael, et al. (författare)
  • Acoustic trapping of cells in a microfluidic format
  • 2005
  • Ingår i: Proceedings of µTAS 2005 Conference. ; 1, s. 515-517
  • Konferensbidrag (refereegranskat)abstract
    • This paper presents, for the first time, non-contact acoustic trapping of cells in a microfluidic format. The employed acoustic force maintains the cells in the center of a fluidic channel while allowing for perfusion of e.g. nutrients or drugs as well as optical monitoring of the cells. Neural stem cells have been acoustically trapped and tested for viability after 15 minutes of ultrasonic radiation. It is also shown that it is possible to grow yeast cells suspended in an acoustic standing wave while perfusing with cell media.
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29.
  • Evander, Magnus, 1959- (författare)
  • Detection of human papillomavirus : a study of normal cells, cervical intraepithelial neoplasia and cancer of the uterine cervix
  • 1991
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Human papillomavirus (HPV) infections of the genital tract are now recognized to be among the most prevalent sexually transmitted diseases and also a contributing factor to some cancers of the lower genital tract of women and men. Presence of HPV in a clinical specimen is confined to detection of the HPV genome by DNA hybridization techniques.In this thesis, the commonly used DNA hybridization techniques Southern blot and filter in situ hybridization (FISH), were first used for detection of genital HPV infection. In order to increase and simplify the detection of HPV in clinical specimens a more sensitive technique, the polymerase chain reaction (PCR) was subsequently utilized.For type-specific amplificaiton of HPV 6, 16, 18 and 33 by PCR, oligonucleotide primers located in the E6 and E7 regions of the HPV genome were selected. They were found to specifically amplify the four types. To be able to amplify a broad spectrum of genital HPV types, general primers located in the E7 and El region of the HPV genome, were designed and evaluated. They were found to amplify a wide range of genital HPV types. To further increase the sensitivity and specificity, a two-step PCR using general primers, was assembled and evaluated against a one-step PCR on cervical scrapes from young women in a population-based study. The two-step PCR increased the sensitivity about three-fold compared to the one-step PCR.By Southern blot and FISH, 46% of women with abnormal Papanicolaou (Pap) smears were shown to carry HPV DNA. Of the women analysed by Southern blot, 39 % harboured HPV DNA and 25 % proved HPV 16 positive. Of the samples analysed with FISH, 27 % contained HPV DNA, compared to 11 % of samples from a group of reference women with normal cytology. With the Southern blot technique, HPV DNA was detected in 66% of women with cervical intraepithelial neoplasia grade III (CIN III) lesions. Fifty-four percent of the women with CIN III lesions were positive for HPV 16 DNA.By type-specific PCR, 12 out of 13 women with cervical squamous carcinoma were shown to carry HPV 16 and/or 18. Among women with adenosquamous carcinoma of the cervix, HPV 18 was the most prevalent type (26%) but HPV 16 was also found in a proportion of the women(15 %). Nine of 13 premenopausal cases with cervical adenocarcinoma were HPV positive compared to only 2 of 13 postmenopausal cases (p< 0.015). HPV 16 DNA was detected in 48%of women with cervical intraepithelial neoplasia (CIN), by the use of type-specific PCR.Three different groups of women with normal cytology were studied. Among women attending a family planning clinic in Kenya, 19% were shown to carry HPV virus, by the use of general primers. HPV 16 was found in 5.2% of these women and HPV 18 in 3.9%. In anothergroup of women, attending the gynecological department in Umeå, HPV 16 DNA was detected in 21 % by type-specific PCR. However, if consideration was taken to the medical status of the women, only 10% of women without any medical history were HPV 16 DNA positive, versus 54% of women with diseases and women with a relative progesterone dominance. Finally, by use of a two-step PCR using general primers, 20% of young women from Umeå taking part in a population-based study were demonstrated to carry HPV DNA. The most prevalent types were HPV 6 (2.0%) and HPV 16(2.7%). Among the women in this study with normal cytology, 19%were HPV positive.
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30.
  • Evander, Magnus, et al. (författare)
  • Milder winters in northern Scandinavia may contribute to larger outbreaks of haemorrhagic fever virus
  • 2009
  • Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 2
  • Tidskriftsartikel (refereegranskat)abstract
    • The spread of zoonotic infectious diseases may increase due to climate factors such as temperature, humidity and precipitation. This is also true for hantaviruses, which are globally spread haemorrhagic fever viruses carried by rodents. Hantaviruses are frequently transmitted to humans all over the world and regarded as emerging viral diseases. Climate variations affect the rodent reservoir populations and rodent population peaks coincide with increased number of human cases of hantavirus infections. In northern Sweden, a form of haemorrhagic fever called nephropathia epidemica (NE), caused by the Puumala hantavirus (PUUV) is endemic and during 2006-2007 an unexpected, sudden and large outbreak of NE occurred in this region. The incidence was 313 cases/100,000 inhabitants in the most endemic areas, and from January through March 2007 the outbreak had a dramatic and sudden start with 474 cases in the endemic region alone. The PUUV rodent reservoir is bank voles and immediately before and during the peak of disease outbreak the affected regions experienced extreme climate conditions with a record-breaking warm winter, registering temperatures 6-9 degrees C above normal. No protective snow cover was present before the outbreak and more bank voles than normal came in contact with humans inside or in close to human dwellings. These extreme climate conditions most probably affected the rodent reservoir and are important factors for the severity of the outbreak.
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31.
  • Evander, Mikael, et al. (författare)
  • Noninvasive acoustic cell trapping in a microfluidic perfusion system for online bioassays
  • 2007
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 79:7, s. 2984-2991
  • Tidskriftsartikel (refereegranskat)abstract
    • Techniques for manipulating, separating, and trapping particles and cells are highly desired in today's bioanalytical and biomedical field. The microfluidic chip-based acoustic noncontact trapping method earlier developed within the group now provides a flexible platform for performing cell- and particle-based assays in continuous flow microsystems. An acoustic standing wave is generated in etched glass channels (600x61 microm2) by miniature ultrasonic transducers (550x550x200 microm3). Particles or cells passing the transducer will be retained and levitated in the center of the channel without any contact with the channel walls. The maximum trapping force was calculated to be 430+/-135 pN by measuring the drag force exerted on a single particle levitated in the standing wave. The temperature increase in the channel was characterized by fluorescence measurements using rhodamine B, and levels of moderate temperature increase were noted. Neural stem cells were acoustically trapped and shown to be viable after 15 min. Further evidence of the mild cell handling conditions was demonstrated as yeast cells were successfully cultured for 6 h in the acoustic trap while being perfused by the cell medium at a flowrate of 1 microL/min. The acoustic microchip method facilitates trapping of single cells as well as larger cell clusters. The noncontact mode of cell handling is especially important when studies on nonadherent cells are performed, e.g., stem cells, yeast cells, or blood cells, as mechanical stress and surface interaction are minimized. The demonstrated acoustic trapping of cells and particles enables cell- or particle-based bioassays to be performed in a continuous flow format.
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32.
  • Evander, Magnus, et al. (författare)
  • Puumala hantavirus viremia diagnosed by real-time reverse transcriptase PCR using samples from patients with hemorrhagic fever and renal syndrome
  • 2007
  • Ingår i: Journal of Clinical Microbiology. - : American Society for Microbiology. - 0095-1137 .- 1098-660X. ; 45:8, s. 2491-2497
  • Tidskriftsartikel (refereegranskat)abstract
    • Puumala virus (PUUV) is the endemic hantavirus in northern Sweden and causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome. There is a need for fast and reliable diagnostics to differentiate the disease from other infections. By aligning virus RNA sequences isolated from 11 different bank voles and one human patient, we designed a real-time reverse transcriptase (RT) PCR method for detection of PUUV RNA. The real-time RT-PCR assay showed linearity from 20 to 2 x 10(6) virus copies with a correlation coefficient above 0.98 to 0.99 for all experiments. The detection threshold for PUUV cDNA was two copies per reaction. A two-step qualitative RT-PCR to detect PUUV RNA showed 100% concordance with the real-time RT-PCR assay. PUUV RNA viremia was detected in 33 of 34 PUUV immunoglobulin M (IgM)-positive patients with typical clinical NE disease from the region of endemicity. One PUUV IgM-negative sample had PUUV RNA, and 4 days later, the patient was IgM positive. Of samples with indeterminate IgM, 43% were PUUV RNA positive. The kinetics of antibody titers and PUUV viremia were studied, and five of six NE patients displayed a decrease in PUUV viremia a few days after disease outbreak coupled with an increase in PUUV IgM and IgG. In one patient with continuously high PUUV RNA levels but low IgM and no IgG response, the infection was lethal. These findings demonstrated that real-time RT-PCR is a useful method for diagnosis of PUUV viremia and for detecting PUUV RNA at early time points, before the appearance of IgM antibodies.
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33.
  • Evander, Magnus, et al. (författare)
  • Seroprevalence and Risk Factors of Inkoo Virus in Northern Sweden
  • 2016
  • Ingår i: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 0002-9637 .- 1476-1645. ; 94:5, s. 1103-1106
  • Tidskriftsartikel (refereegranskat)abstract
    • The mosquito-borne Inkoo virus (INKV) is a member of the California serogroup in the family Bunyaviridae, genus Orthobunyavirus These viruses are associated with fever and encephalitis, although INKV infections are not usually reported and the incidence is largely unknown. The aim of the study was to determine the prevalence of anti-INKV antibodies and associated risk factors in humans living in northern Sweden. Seroprevalence was investigated using the World Health Organization Monitoring of Trends and Determinants in Cardiovascular Disease study, where a randomly selected population aged between 25 and 74 years (N = 1,607) was invited to participate. The presence of anti-INKV IgG antibodies was determined by immunofluorescence assay. Seropositivity for anti-INKV was significantly higher in men (46.9%) than in women (34.8%; P < 0.001). In women, but not in men, the prevalence increased somewhat with age (P = 0.06). The peak in seropositivity was 45-54 years for men and 55-64 years for women. Living in rural areas was associated with a higher seroprevalence. In conclusion, the prevalence of anti-INKV antibodies was high in northern Sweden and was associated with male sex, older age, and rural living. The age distribution indicates exposure to INKV at a relatively early age. These findings will be important for future epidemiological and clinical investigations of this relatively unknown mosquito-borne virus.
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34.
  • Gwon, Yong-Dae, et al. (författare)
  • Antiviral Activity of Benzavir-2 against Emerging Flaviviruses
  • 2020
  • Ingår i: Viruses. - : MDPI. - 1999-4915. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Most flaviviruses are arthropod-borne viruses, transmitted by either ticks or mosquitoes, and cause morbidity and mortality worldwide. They are endemic in many countries and have recently emerged in new regions, such as the Zika virus (ZIKV) in South-and Central America, the West Nile virus (WNV) in North America, and the Yellow fever virus (YFV) in Brazil and many African countries, highlighting the need for preparedness. Currently, there are no antiviral drugs available to treat flavivirus infections. We have previously discovered a broad-spectrum antiviral compound, benzavir-2, with potent antiviral activity against both DNA- and RNA-viruses. Our purpose was to investigate the inhibitory activity of benzavir-2 against flaviviruses. We used a ZIKV ZsGreen-expressing vector, two lineages of wild-type ZIKV, and other medically important flaviviruses. Benzavir-2 inhibited ZIKV derived reporter gene expression with an EC50 value of 0.8 +/- 0.1 µM. Furthermore, ZIKV plaque formation, progeny virus production, and viral RNA expression were strongly inhibited. In addition, 2.5 µM of benzavir-2 reduced infection in vitro in three to five orders of magnitude for five other flaviviruses: WNV, YFV, the tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. In conclusion, benzavir-2 was a potent inhibitor of flavivirus infection, which supported the broad-spectrum antiviral activity of benzavir-2.
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35.
  • Gylfe, Åsa, et al. (författare)
  • Mosquitoborne Sindbis Virus Infection and Long-Term Illness
  • 2018
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 24:6, s. 1141-1142
  • Tidskriftsartikel (refereegranskat)abstract
    • An unexpected human outbreak of the mosquitoborne Sindbis virus occurred in a previously nonendemic area of Sweden. At follow-up, 6-8 months after infection, 39% of patients had chronic arthralgia that affected their daily activities. Vectorborne infections may disseminate rapidly into new areas and cause acute and chronic disease.
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36.
  • Hardestam, Jonas, et al. (författare)
  • Antiviral effect of human saliva against hantavirus.
  • 2008
  • Ingår i: Journal of medical virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 80:12, s. 2122-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome are zoonotic diseases caused by rodent borne hantaviruses. Transmission to humans occurs usually by inhalation of aerozolized virus-contaminated rodent excreta. Although human-to-human transmission of Andes hantavirus has been observed, the mode of transmission is currently not known. Saliva from Puumala hantavirus (PUUV)-infected patients was shown recently to contain viral RNA. To test if human saliva interferes with hantavirus replication, the effect of saliva and salivary proteins on hantavirus replication was studied. It was observed that saliva from healthy individuals reduced Hantaan hantavirus (HTNV) infectivity, although not completely. Furthermore, HTNV was resistant against the antiviral capacity of histatin 5, lysozyme, lactoferrin, and SLPI, but was inhibited by mucin. Inoculation of bank voles (Myodes glareolus) with HFRS-patient saliva, positive for PUUV-RNA, did not induce sero-conversion. In conclusion, no evidence of infectious virus in patient saliva was found. However, the in vitro experiments showed that HTNV, the prototype hantavirus, is insensitive to several antiviral salivary proteins, and is partly resistant to the antiviral effect of saliva. It therefore remains to be shown if human saliva might contain infectious virions early during infection, that is, before seroconversion.
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37.
  • Hassan, Osama Ahmed, et al. (författare)
  • A need for One Health approach : lessons learned from outbreaks of Rift Valley fever in Saudi Arabia and Sudan
  • 2014
  • Ingår i: Infection Ecology & Epidemiology. - : CoAction Publishing. - 2000-8686. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Rift Valley fever (RVF) is an emerging viral zoonosis that impacts human and animal health. It is transmitted from animals to humans directly through exposure to blood, body fluids, or tissues of infected animals or via mosquito bites. The disease is endemic to Africa but has recently spread to Saudi Arabia and Yemen. Our aim was to compare two major outbreaks of RVF in Saudi Arabia (2000) and Sudan (2007) from a One Health perspective.METHODS: Using the terms 'Saudi Arabia', 'Sudan', and 'RVF', articles were identified by searching PubMed, Google Scholar, and web pages of international organizations as well as local sources in Saudi Arabia and Sudan.RESULTS: The outbreak in Saudi Arabia caused 883 human cases, with a case fatality rate of 14% and more than 40,000 dead sheep and goats. In Sudan, 698 human cases of RVF were recognized (case fatality, 31.5%), but no records of affected animals were available. The ecology and environment of the affected areas were similar with irrigation canals and excessive rains providing an attractive habitat for mosquito vectors to multiply. The outbreaks resulted in livestock trade bans leading to a vast economic impact on the animal market in the two countries. The surveillance system in Sudan showed a lack of data management and communication between the regional and federal health authorities, while in Saudi Arabia which is the stronger economy, better capacity and contingency plans resulted in efficient countermeasures. Studies of the epidemiology and vectors were also performed in Saudi Arabia, while in Sudan these issues were only partly studied.CONCLUSION: We conclude that a One Health approach is the best option to mitigate outbreaks of RVF. Collaboration between veterinary, health, and environmental authorities both on national and regional levels is needed.
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38.
  • Hassan, Osama Ahmed, et al. (författare)
  • The 2007 rift valley Fever outbreak in Sudan
  • 2011
  • Ingår i: PLoS Neglected Tropical Diseases. - San Francisco, CA : Public Library of Science. - 1935-2727 .- 1935-2735. ; 5:9
  • Forskningsöversikt (refereegranskat)abstract
    • Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF.
  •  
39.
  • Hassan, Osama Ahmed, 1972-, et al. (författare)
  • The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks
  • 2017
  • Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2727 .- 1935-2735. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Rift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants' food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased.
  •  
40.
  • Hellgren, Fredrika, et al. (författare)
  • Modulation of innate immune response to mRNA vaccination after SARS-CoV-2 infection or sequential vaccination in humans
  • 2024
  • Ingår i: JCI Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708. ; 9:9
  • Tidskriftsartikel (refereegranskat)abstract
    • mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine. Prior infection conferred significantly stronger induction of proinflammatory and type I IFN-related gene signatures, serum cytokines, and monocyte expansion after the prime vaccination. The response to the second vaccination further increased the magnitude of the early innate response in both study groups. The third vaccination did not further increase vaccine-induced inflammation. In vitro stimulation of PBMCs with TLR ligands showed no difference in cytokine responses between groups, or before or after prime vaccination, indicating absence of a trained immunity effect. We observed that levels of preexisting antigen-specific CD4 T cells, antibody, and memory B cells correlated with elements of the early innate response to the first vaccination. Our data thereby indicate that preexisting memory formed by infection may augment the innate immune activation induced by mRNA vaccines.
  •  
41.
  • Hoffman, Tove, et al. (författare)
  • Alkhurma Hemorrhagic Fever Virus RNA in Hyalomma rufipes Ticks Infesting Migratory Birds, Europe and Asia Minor
  • 2018
  • Ingår i: Emerging Infectious Diseases. - Atlanta, United States : U.S. Department of Health and Human Services * Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 24:5, s. 879-882
  • Tidskriftsartikel (refereegranskat)abstract
    • Alkhurma hemorrhagic fever virus RNA was detected in immature Hyalomma rufipes ticks infesting northward migratory birds caught in the North Mediterranean Basin. This finding suggests a role for birds in the ecology of the Alkhurma hemorrhagic fever virus and a potential mechanism for dissemination to novel regions. Increased surveillance is warranted.
  •  
42.
  • Ianevski, Aleksandr, et al. (författare)
  • Novel activities of safe-in-human broad-spectrum antiviral agents
  • 2018
  • Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 154, s. 174-182
  • Tidskriftsartikel (refereegranskat)abstract
    • According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-inhuman antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.
  •  
43.
  • Islam, Koushikul, 1985- (författare)
  • Identification and evaluation of antiviral compounds targeting Rift Valley fever virus
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rift Valley fever virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease Rift Valley fever (RVF). RVFV causes significant morbidity and mortality in humans and livestock throughout Africa and the Arabian Peninsula. RVFV is an emerging virus and is capable of infecting a broad range of mosquito species distributed around the world, so it poses a potential threat globally. A wide range of livestock animals (e.g. sheep, goats, cows, and camels) and some wild animals become highly affected by RVFV. In humans, RVFV infection presents as an acute self-limiting febrile illness that may lead to more severe hemorrhagic fever and encephalitis. The severity of the disease is mostly dependent on age and the species of mammal, but other factors are also important.There are no licensed RVFV vaccines for humans, and there is a lack of effective antiviral drugs. Moreover, due to the severe pathogenicity, higher-level facilities are needed―biosafety level 3 (BSL-3) or more―to work with RVFV, which makes antiviral drug development more challenging. Because RVFV causes severe disease in Africa and the Arabian Peninsula, and has the potential to spread globally, it is essential that safe, efficient antiviral drugs against this virus are developed.The previously reported antiviral compound benzavir-2 inhibits the replication of several DNA viruses, i.e. human adenoviruses, herpes simplex virus (HSV) type 1, and HSV type 2, indicating a broadranging activity. We wanted to evaluate whether benzavir-2 had an effect against the RNA virus RVFV. For these and subsequent studies, we used a recombinant, modified RVFV strain with a deleted NSs gene, which was replaced by a reporter gene (rRVFVΔNSs::Katushka), enabling the studies to be conducted under BSL-2 conditions. The NSs gene is the main virulence factor for RVFV and without it, RVFV become less pathogenic. The reporter gene made it possible for us to quantify infection with the help of the red fluorescent protein. We found that benzavir-2 effectively inhibited RVFV infection in cell culture at an effective concentration showing 50% inhibition (EC50) of 0.6 μM. Benzavir-2 also inhibited the production of progeny virus. When we studied the pharmacokinetic properties, we found that benzavir-2 had good in vitro solubility, permeability, and metabolic stability. When we investigated the oral bioavailability in mice by administering benzavir-2 in peanut butter pellets, high systemic distribution was observed without any adverse toxic effects. Benzavir-2 thus inhibited RVFV infection in cell culture and showed excellent pharmacokinetic properties, suggesting the possibility of evaluating its effectiveness in an animal model. Since benzavir-2 has a broad effect against both RNA and DNA viruses, we speculated that the antiviral mechanism affects cellular targets.We also wanted to explore a large number of small chemical compounds with unknown properties and identify any anti-RVFV activities. Thus, we developed a whole-cell-based high-throughput reporter-based assay, and screened 28,437 small chemical compounds. The assay was established after optimization of several parameters. After primary and secondary screening, we identified 63 compounds that inhibited RVFV infection by 60% at a concentration of 3.12 μM and showed ≥ 50% cell viability at 25 μM. After a dose-dependent screening of these 63 compounds, several compounds were identified with highly efficient anti-RVFV properties. Finally, N1-(2-(biphenyl-4-yloxy)ethyl)propane-1,3-diamine (compound 1) was selected as the lead compound. We performed a structure-activity relationship (SAR) analysis of compound 1 by replacing and changing component after component of the chemical compound to see how this affected the antiviral activity. After the SAR analysis, the antiviral activity did not change, but we could improve the cytotoxicity profile. Our studies suggested that the improved compound, 13a, might be targeting the early phase of the RVFV lifecycle.In conclusion, we developed an efficient and reliable screening method that creates possibilities for discovering and developing antivirals against RVFV under BSL-2 conditions. We also identified several chemical compounds with anti-RVFV activities, which might lead to development of therapies for RVFV infection.
  •  
44.
  • Islam, Koushikul, 1985-, et al. (författare)
  • Structural Modifications and Biological Evaluations of Rift Valley Fever Virus Inhibitors Identified from Chemical Library Screening
  • 2022
  • Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:8, s. 6854-6868
  • Tidskriftsartikel (refereegranskat)abstract
    • The Rift Valley fever virus (RVFV) is an emerging high-priority pathogen endemic in Africa with pandemic potential. There is no specific treatment or approved antiviral drugs for the RVFV. We previously developed a cell-based high-throughput assay to screen small molecules targeting the RVFV and identified a potential effective antiviral compound (1-N-(2-(biphenyl-4-yloxy)ethyl)propane-1,3-diamine) as a lead compound. Here, we investigated how structural modifications of the lead compound affected the biological properties and the antiviral effect against the RVFV. We found that the length of the 2-(3-aminopropylamino)ethyl chain of the compound was important for the compound to retain its antiviral activity. The antiviral activity was similar when the 2-(3-aminopropylamino)ethyl chain was replaced with a butyl piperazine chain. However, we could improve the cytotoxicity profile of the lead compound by changing the phenyl piperazine linker from the para-position (compound 9a) to the meta-position (compound 13a). Results from time-of-addition studies suggested that compound 13a might be active during virus post-entry and/or the replication phase of the virus life cycle and seemed to affect the K+ channel. The modifications improved the properties of our lead compound, and our data suggest that 13a is a promising candidate to evaluate further as a therapeutic agent for RVFV infection.
  •  
45.
  • Islam, Md. Koushikul, et al. (författare)
  • Anti-Rift Valley fever virus activity in vitro, pre-clinical pharmacokinetics and oral bioavailability of benzavir-2, a broad-acting antiviral compound
  • 2018
  • Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Rift Valley fever virus (RVFV) is a mosquito-borne hemorrhagic fever virus affecting both humans and animals with severe morbidity and mortality and is classified as a potential bioterror agent due to the possible aerosol transmission. At present there is no human vaccine or antiviral therapy available. Thus, there is a great need to develop new antivirals for treatment of RVFV infections. Benzavir-2 was previously identified as potent inhibitor of human adenovirus, herpes simplex virus type 1, and type 2. Here we assess the anti-RVFV activity of benzavir-2 together with four structural analogs and determine pre-clinical pharmacokinetic parameters of benzavir-2. In vitro, benzavir-2 efficiently inhibited RVFV infection, viral RNA production and production of progeny viruses. In vitro, benzavir-2 displayed satisfactory solubility, good permeability and metabolic stability. In mice, benzavir-2 displayed oral bioavailability with adequate maximum serum concentration. Oral administration of benzavir-2 formulated in peanut butter pellets gave high systemic exposure without any observed toxicity in mice. To summarize, our data demonstrated potent anti-RVFV activity of benzavir-2 in vitro together with a promising pre-clinical pharmacokinetic profile. This data support further exploration of the antiviral activity of benzavir-2 in in vivo efficacy models that may lead to further drug development for human use.
  •  
46.
  • Islam, Md. Koushikul, et al. (författare)
  • High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection
  • 2016
  • Ingår i: Journal of Biomolecular Screening. - : Sage Publications. - 1087-0571 .- 1552-454X. ; 21:4, s. 354-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by 80%, with 50% cell viability at 50 mu M concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with 60% inhibition of RVFV infection at 3.12 mu M compound concentration and 50% cell viability at 25 mu M were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection.
  •  
47.
  • Khalil, Hussein, et al. (författare)
  • Population Dynamics of Bank Voles Predicts Human Puumala Hantavirus Risk
  • 2019
  • Ingår i: EcoHealth. - : Springer. - 1612-9202 .- 1612-9210. ; 16:3, s. 545-557
  • Tidskriftsartikel (refereegranskat)abstract
    • Predicting risk of zoonotic diseases, i.e., diseases shared by humans and animals, is often complicated by the population ecology of wildlife host(s). We here demonstrate how ecological knowledge of a disease system can be used for early prediction of human risk using Puumala hantavirus (PUUV) in bank voles (Myodes glareolus), which causes Nephropathia epidemica (NE) in humans, as a model system. Bank vole populations at northern latitudes exhibit multiannual fluctuations in density and spatial distribution, a phenomenon that has been studied extensively. Nevertheless, existing studies predict NE incidence only a few months before an outbreak. We used a time series on cyclic bank vole population density (1972–2013), their PUUV infection rates (1979–1986; 2003–2013), and NE incidence in Sweden (1990–2013). Depending on the relationship between vole density and infection prevalence (proportion of infected animals), either overall density of bank voles or the density of infected bank voles may be used to predict seasonal NE incidence. The density and spatial distribution of voles at density minima of a population cycle contribute to the early warning of NE risk later at its cyclic peak. When bank voles remain relatively widespread in the landscape during cyclic minima, PUUV can spread from a high baseline during a cycle, culminating in high prevalence in bank voles and potentially high NE risk during peak densities.
  •  
48.
  • Khalil, Hussein, et al. (författare)
  • Selective predation on hantavirus-infected voles by owls and confounding effects from landscape properties
  • 2016
  • Ingår i: Oecologia. - : Springer Science and Business Media LLC. - 0029-8549 .- 1432-1939. ; 181:2, s. 597-606
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been suggested that predators may protect human health through reducing disease-host densities or selectively preying on infected individuals from the population. However, this has not been tested empirically. We hypothesized that Tengmalm's owl (Aegolius funereus) selectively preys on hantavirus-infected individuals of its staple prey, the bank vole (Myodes glareolus). Bank voles are hosts of Puumala hantavirus, which causes a form of hemorrhagic fever in humans. Selective predation by owls on infected voles may reduce human disease risk. We compared the prevalence of anti-Puumala hantavirus antibodies (seroprevalence), in bank voles cached by owls in nest boxes to seroprevalence in voles trapped in closed-canopy forest around each nest box. We found no general difference in seroprevalence. Forest landscape structure could partly account for the observed patterns in seroprevalence. Only in more connected forest patches was seroprevalence in bank voles cached in nest boxes higher than seroprevalence in trapped voles. This effect disappeared with increasing forest patch isolation, as seroprevalence in trapped voles increased with forest patch isolation, but did not in cached voles. Our results suggest a complex relationship between zoonotic disease prevalence in hosts, their predators, and landscape structure. Some mechanisms that may have caused the seroprevalence patterns in our results include higher bank vole density in isolated forest patches. This study offers future research potential to shed further light on the contribution of predators and landscape properties to human health.
  •  
49.
  • Kirui, Jared, et al. (författare)
  • The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry
  • 2021
  • Ingår i: Cells. - : MDPI. - 2073-4409. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.
  •  
50.
  • Lindgren, Therese, 1977-, et al. (författare)
  • Longitudinal analysis of the human T cell response during acute hantavirus infection
  • 2011
  • Ingår i: Journal of Virology. - Baltimore : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 85:19, s. 10252-10260
  • Tidskriftsartikel (refereegranskat)abstract
    • Longitudinal studies of T cell immune responses during viral infections in humans are essential for our understanding of how effector T cell responses develop, clear infection, and provide long-lasting immunity. Here, following an outbreak of a Puumala hantavirus infection in the human population, we longitudinally analyzed the primary CD8 T cell response in infected individuals from the first onset of clinical symptoms until viral clearance. A vigorous CD8 T cell response was observed early following the onset of clinical symptoms, determined by the presence of high numbers of Ki67(+)CD38(+)HLA-DR(+) effector CD8 T cells. This response encompassed up to 50% of total blood CD8 T cells, and it subsequently contracted in parallel with a decrease in viral load. Expression levels of perforin and granzyme B were high throughout the initial T cell response and likewise normalized following viral clearance. When monitoring regulatory components, no induction of regulatory CD4 or CD8 T cells was observed in the patients during the infection. However, CD8 as well as CD4 T cells exhibited a distinct expression profile of inhibitory PD-1 and CTLA-4 molecules. The present results provide insight into the development of the T cell response in humans, from the very onset of clinical symptoms following a viral infection to resolution of the disease.
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