| 1. |
- Iheozor-Ejiofor, Rommel, et al.
(författare)
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Neutralizing Antibody Titers in Hospitalized Patients with Acute Puumala Orthohantavirus Infection Do Not Associate with Disease Severity
- 2022
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:5
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Tidskriftsartikel (refereegranskat)abstract
- Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.
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| 2. |
- Bulanova, Daria, et al.
(författare)
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Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins
- 2017
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.
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| 3. |
- Bösl, Korbinian, et al.
(författare)
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Common Nodes of Virus-Host Interaction Revealed Through an Integrated Network Analysis
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape.
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| 4. |
- Erra, Elina O, et al.
(författare)
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A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines
- 2012
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 55:6, s. 825-834
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:A significant part of the world population lives in areas with endemic Japanese encephalitis (JE). For travelers from nonendemic countries, Vero cell-derived vaccine (JE-VC; Ixiaro) has replaced traditional mouse brain-derived vaccines (JE-MB) associated with safety concerns. The 2 vaccines are derived from different viral strains: JE-VC from the SA14-14-2 strain and JE-MB from the Nakayama strain. No data exist regarding whether JE-VC can be used to boost immunity after a primary series of JE-MB; therefore, a primary series of JE-VC has been recommended to all travelers regardless of previous vaccination history.METHODS:One hundred twenty travelers were divided into 4 groups: Volunteers with no prior JE vaccination received primary immunization with (group 1) JE-MB or (group 2) JE-VC, and those primed with JE-MB received a single booster dose of (group 3) JE-MB or (group 4) JE-VC. Immune responses were tested before and 4-8 weeks after vaccination using plaque reduction neutralization test (PRNT) against both vaccine strains.RESULTS:In vaccine-naive travelers, the vaccination response rate for test strains Nakayama and SA14-14-2 was 100% and 87% after primary vaccination with JE-MB and 87% and 94% after JE-VC, respectively. Antibody levels depended on the target virus, with higher titers against homologous than heterologous PRNT(50) target strain (P < .001). In travelers primed with JE-MB, vaccination response rates were 91% and 91%, and 98% and 95% after a booster dose of JE-MB or JE-VC, respectively. Subgroup analysis revealed that a higher proportion of primed (98%/95%) than nonprimed (39%/42%) volunteers responded to a single dose of JE-VC (P < .001).CONCLUSIONS:A single dose of JE-VC effectively boosted immunity in JE-MB-primed travelers. Current recommendations should be reevaluated.CLINICAL TRIALS REGISTRATION:NCT01386827.
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| 5. |
- Erra, Elina O., et al.
(författare)
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Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis : A two-year follow-up study
- 2013
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 32:1, s. 119-123
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Tidskriftsartikel (refereegranskat)abstract
- Background: The inactivated Vero cell-derived vaccine (JE-VC, IXIARO) has replaced the traditional mouse brain-derived preparations (JE-MB) in travelers' vaccinations against Japanese encephalitis. We showed recently that a single JE-VC dose efficiently boosts immunity in JE-MB-primed vaccinees, and that JE-VC elicits cross-protective immunity against non-vaccine genotypes, including the emerging genotype I. While these studies only provided short-term data, the present investigation evaluates the longevity of seroprotection in the same volunteers.Methods:The study comprised 48 travelers who had received (1) JE-VC primary series, (2) JE-MB primary series followed by a single JE-VC booster dose, or (3) JE-MB primary series and a single JE-MB booster dose. Serum samples were collected two years after the last vaccine dose, and evaluated with the plaque-reduction neutralization test against seven Japanese encephalitis virus strains representing genotypes I-IV. PRNT50 titers >= 10 were considered protective.Results:Two years after the primary series with JE-VC, 87-93% of the vaccinees proved to be cross-protected against test strains representing genotypes II-IV and 73% against those of genotype I. After a single homologous or heterologous booster dose to JE-MB-primed subjects, the two-year seroprotection rates against genotype I-IV strains were 89-100%.Conclusions:After JE-VC primary series, seroprotection appeared to wane first against genotype I. The first booster should not be delayed beyond two years. In JE-MB-primed subjects, a single JE-VC booster provided cross-protective immunity against genotype I-IV strains in almost all vaccinees, suggesting an interval of two years or even longer for the second booster. These data further support the use of a single JE-VC dose for boosting JE-MB immunity.
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| 6. |
- Erra, Elina O, et al.
(författare)
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Cross-protective capacity of Japanese encephalitis (JE) vaccines against circulating heterologous JE virus genotypes
- 2013
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 56:2, s. 267-270
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Tidskriftsartikel (refereegranskat)abstract
- Current Japanese encephalitis vaccines are derived from strains of genotype III, yet heterologous genotypes are emerging in endemic areas. Inactivated vaccines given to European travelers were found to elicit protective levels of neutralizing antibodies against heterologous strains of genotypes I-IV.
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| 7. |
- Escadafal, Camille, et al.
(författare)
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Second External Quality Assurance Study for the Serological Diagnosis of Hantaviruses in Europe
- 2012
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Ingår i: PLoS Neglected Tropical Diseases. - : Public Library of Science (PLoS). - 1935-2735. ; 6:4, s. e1607-
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Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses are endemic throughout the world and hosted by rodents and insectivores. Two human zoonoses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are caused by hantaviruses and case fatality rates have reached 12% for HFRS and 50% for HPS in some outbreaks. Symptomatic hantavirus infections in Europe are summarised as HFRS mainly due to Puumala, Dobrava-Belgrade and Saaremaa virus. While HFRS has an overall low incidence in Europe, the number of cases varies from 100 per year in all Eastern and Southern Europe up to 1,000 per year only in Finland. To assess the quality of hantavirus diagnostics, the European Network for the Diagnostics of 'Imported'' Viral Diseases (ENIVD) organised a first external quality assurance (EQA) in 2002. The purpose of this second EQA study is to collect updated information on the efficiency and accurateness of hantavirus serological methods applied by expert laboratories. A serum panel of 14 samples was sent to 28 participants in Europe of which 27 sent results. Performance in hantavirus diagnosis varied not only on the method used but also on the laboratories and the subclass of antibodies tested. Commercial and in-house assays performed almost equally. Enzyme immunoassays were mainly used but did not show the best performances while immunoblot assays were the less employed and showed overall better performances. IgM antibodies were not detected in 61% of the positive IgM samples and IgM detection was not performed by 7% of the laboratories indicating a risk of overlooking acute infections in patients. Uneven performances using the same method is indicating that there is still a need for improving testing conditions and standardizing protocols.
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| 8. |
- Evander, Magnus, et al.
(författare)
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Seroprevalence and Risk Factors of Inkoo Virus in Northern Sweden
- 2016
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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
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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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| 9. |
- Hepojoki, Satu, et al.
(författare)
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Competitive Homogeneous Immunoassay for Rapid Serodiagnosis of Hantavirus Disease
- 2015
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Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 53:7, s. 2292-2297
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we describe a competitive homogeneous immunoassay that makes use of Forster resonance energy transfer (FRET) in rapid detection of pathogen-specific antibodies. The assay principle is based on competition between a monoclonal antibody (MAb) and serum antibodies to a given antigen. In the assay, named competitive FRET immunoassay (CFRET-IA), the FRET signal is induced if MAb carrying a donor label binds to an acceptor-labeled antigen. Specific antibodies in serum compete for antigen binding, resulting in reduced FRET signal. The proof-of-principle for the assay was obtained using donor-labeled Puumala virus nucleocapsid protein (PUUV-N) and acceptor-labeled anti-PUUV-N MAb. The assay was evaluated by analyzing 329 clinical samples comprising 101 from individuals with acute PUUV infection, 42 from individuals with past infection, and 186 from individuals with PUUV-seronegative sera, and the results were compared to those of reference tests. The rapid serodiagnostic test we introduced herein performed with 100% sensitivity and 99% specificity for diagnosing acute hantavirus disease.
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| 10. |
- Ianevski, Aleksandr, et al.
(författare)
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Novel activities of safe-in-human broad-spectrum antiviral agents
- 2018
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Ingår i: Antiviral Research. - : Elsevier. - 0166-3542 .- 1872-9096. ; 154, s. 174-182
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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.
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| 11. |
- Iheozor-Ejiofor, Rommel Paneth, et al.
(författare)
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Vaccinia virus-free rescue of fluorescent replication-defective vesicular stomatitis virus and pseudotyping with Puumala virus glycoproteins for use in neutralization tests
- 2016
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 97, s. 1052-1059
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Tidskriftsartikel (refereegranskat)abstract
- Puumala virus (PUUV) grows slowly in cell culture. To study antigenic properties of PUUV, an amenable method for their expression would be beneficial. To achieve this, a replication-defective recombinant vesicular stomatitis virus, rVSV Delta G*EGFP, was rescued using BSRT7/5 and encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES)-enabled rescue plasmids. Using these particles, pseudotypes bearing PUUV Sotkamo strain glycoproteins were produced, with titres in the range 10(5)-10(8), and were used in pseudotype focus reduction neutralization tests (pFRNTs) with neutralizing monoclonal antibodies and patient sera. The results were compared with those from orthodox focus reduction neutralization tests (oFRNTs) using native PUUV with the same samples and showed a strong positive correlation (r(s)=0.82) between the methods. While developing the system we identified three amino acids which were mutated in the Vero E6 cell culture adapted PUUV prototype Sotkamo strain sequence, and changing these residues was critical for expression and neutralizing antibody binding of PUUV glycoproteins.
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| 12. |
- Jaaskelainen, Anne J., et al.
(författare)
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Development and Evaluation of a Real-Time RT-qPCR for Detection of Crimean-Congo Hemorrhagic Fever Virus Representing Different Genotypes
- 2014
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Ingår i: Vector Borne and Zoonotic Diseases. - : Mary Ann Liebert. - 1530-3667 .- 1557-7759. ; 14:12, s. 870-872
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Tidskriftsartikel (refereegranskat)abstract
- Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease caused by a nairovirus belonging to family Bunyaviridae. The CCHF virus (CCHFV) can be transmitted to humans by Hyalomma ticks as well as by direct contact with infected body fluids or tissues from viremic livestock or humans. Our aim was to set up a fast RT-qPCR for detection of the different CCHFV genotypes in clinical samples, including an inactivation step to make the sample handling possible in lower biosafety levels (BSL) than BSL-4. This method was evaluated against commercial reference assays and international External Quality Assessment (EQA) samples. The analytical limit of detection for the developed CCHFV-S RT-qPCR was 11 CCHFV genomes per reaction. After exclusion of four dubious samples, we studied 38 CCHFV-positive samples (using reference tests) of which 38 were found positive by CCHFV-S RT-qPCR, suggesting a sensitivity of 100%. CCHFV-S RT q-PCR detected all eight different CCHFV strains representing five different CCHFV genotypes. In conclusion, the CCHFV-S RT-qPCR described in this study was evaluated using various sources of CCHFV samples and shown to be an accurate tool to detect human CCHFV infection caused by different genotypes of the virus.
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| 13. |
- Jääskeläinen, Anne J, et al.
(författare)
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Evidence of ljungan virus specific antibodies in humans and rodents, Finland.
- 2013
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 85:11, s. 2001-2008
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Tidskriftsartikel (refereegranskat)abstract
- Ljungan virus (LV, genus Parechovirus, family Picornaviridae) is considered currently to be a rodent-borne virus. Despite suggested human disease associations, its zoonotic potential remains unclear. To date, LV antibody prevalence in both humans and rodents has not been studied. In this study, two different LV immunofluorescence assays (LV IFAs) were developed with LV genotypes 1 (LV strain 87-012G) and 2 (LV strain 145SLG), and cross-neutralization and -reaction studies were carried out with LV strain 145SLG. Finally, a panel of 37 Finnish sera was screened for anti-LV antibodies using two different LV IFAs (LV 145SLG and LV 87-012G) and a neutralization (NT) assay (LV 145SLG), and 50 samples from Myodes glareolus by LV IFA (LV 145SLG). The LV seroprevalence study showed 38% and 18% positivity in humans and M. glareolus, respectively. LV IFAs and NT assays were compared, and the results were in good agreement. The data are the first evidence of humans and rodents coming into contact with LV in Finland. Additional studies are required in order to acquire a better understanding of the prevalence, epidemiological patterns and possible disease association of LV infections.
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| 14. |
- Kallio, Eva R., et al.
(författare)
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Maternal antibodies contribute to sex-based difference in hantavirus transmission dynamics
- 2013
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Ingår i: Biology Letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 9:6, s. 20130887-
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Tidskriftsartikel (refereegranskat)abstract
- Individuals often differ in their ability to transmit disease and identifying key individuals for transmission is a major issue in epidemiology. Male hosts are often thought to be more important than females for parasite transmission and persistence. However, the role of infectious females, particularly the transient immunity provided to offspring through maternal antibodies (MatAbs), has been neglected in discussions about sex-biased infection transmission. We examined the effect of host sex upon infection dynamics of zoonotic Puumala hantavirus (PUUV) in semi-natural, experimental populations of bank vole (Myodes glareolus). Populations were founded with either females or males that were infected with PUUV, whereas the other sex was immunized against PUUV infection. The likelihood of the next generation being infected was lower when the infected founders were females, underlying the putative importance of adult males in PUUV transmission and persistence in host populations. However, we show that this effect probably results from transient immunity that infected females provide to their offspring, rather than any sex-biased transmission efficiency per se. Our study proposes a potential contrasting nature of female and male hosts in the transmission dynamics of hantaviruses.
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| 15. |
- Levanov, Lev, et al.
(författare)
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Defining of MAbs-neutralizing sites on the surface glycoproteins Gn and Gc of a hantavirus using vesicular stomatitis virus pseudotypes and site-directed mutagenesis
- 2019
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Ingår i: Journal of General Virology. - : MICROBIOLOGY SOC. - 0022-1317 .- 1465-2099. ; 100:2, s. 145-155
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Tidskriftsartikel (refereegranskat)abstract
- Earlier four monoclonal antibodies (MAbs) against surface glycoproteins Gn and Gc of puumala virus (PUUV, genus Orthohantavirus, family Hantaviridae, order Bunyavirales) were generated and for three MAbs with neutralizing capacity the localization of binding epitopes was predicted using pepscan and phage-display techniques. In this work, we produced vesicular stomatitis virus (VSV) particles pseudotyped with the Gn and Gc glycoproteins of PUUV and applied site-directed mutagenesis to dissect the structure of neutralizing epitopes. Replacement of cysteine amino acid (aa) residues with alanines resulted in pseudotype particles with diminished (16 to 18 %) neut-titres; double Cys -> Ala mutants, as well as mutants with bulky aromatic and charged residues replaced with alanines, have shown even stronger reduction in neut-titres (from 25 % to the escape phenotype). In silico modelling of the neut-epitopes supported the hypothesis that these critical residues are located on the surface of viral glycoprotein molecules and thus can be recognized by the antibodies indeed. A similar pattern was observed in experiments with mutant pseudotypes and sera collected from patients suggesting that these neut-epitopes are utilized in a course of human PUUV infection. These data will help understanding the mechanisms of hantavirus neutralization and assist construction of vaccine candidates.
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| 16. |
- Ling, Jiaxin, et al.
(författare)
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Evolution and postglacial colonization of Seewis hantavirus with Sorex araneus in Finland
- 2018
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Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 57, s. 88-97
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Tidskriftsartikel (refereegranskat)abstract
- Hantaviruses have co-existed with their hosts for millions of years. Seewis virus (SWSV), a soricomorph-borne hantavirus, is widespread in Eurasia, ranging from Central Siberia to Western Europe. To gain insight into the phylogeography and evolutionary history of SWSV in Finland, lung tissue samples of 225 common shrews (Sorex araneus) trapped from different parts of Finland were screened for the presence of SWSV RNA. Forty-two of the samples were positive. Partial small (S), medium (M) and large (L) segments of the virus were sequenced, and analyzed together with all SWSV sequences available in Genbank. The phylogenetic analysis of the partial S-segment sequences suggested that all Finnish SWSV strains shared their most recent common ancestor with the Eastern European strains, while the L-segment suggested multiple introductions. The difference between the Land S-segment phylogenies implied that reassortment events play a role in the evolution of SWSV. Of the Finnish strains, variants from Eastern Finland occupied the root position in the phylogeny, and had the highest genetic diversity, supporting the hypothesis that SWSV reached Finland first form the east. During the spread in Finland, the virus has formed three separate lineages, identified here by correlation analysis of genetic versus geographic distance combined with median-joining network analysis. These results support the hypothesis that Finnish SWSV recolonized Finland with its host, the common shrew, from east after the last ice age 12,000-8000 years ago, and then subsequently spread along emerging land bridges towards west or north with the migration and population expansion of its host.
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| 17. |
- Ling, Jiaxin, et al.
(författare)
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Introduction and Dispersal of Sindbis Virus from Central Africa to Europe
- 2019
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Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 93:16
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Tidskriftsartikel (refereegranskat)abstract
- Bird-hosted viruses have the potential to be transported over large areas of the world and to be transmitted in distant geographical regions. Sindbis virus (SINV) is a mosquito-borne alphavirus that is locally amplified in a bird-mosquito enzootic cycle and distributed all over the Old World and Australia/Oceania. Sindbis virus genotype I (SINV-I) is the cause of disease outbreaks in humans in South Africa as well as in northern Europe. To trace the evolutionary history and potential strain-disease association of SINV-I, we sequenced 36 complete genomes isolated from field material in Europe, as well as in Africa and the Middle East, collected over 58 years. These were analyzed together with 30 additional published whole SINV-I genomes using Bayesian analysis. Our results suggested that SINV-I was introduced only once to northern Europe from central Africa, in the 1920s. After its first introduction to Sweden, it spread east and southward on two separate occasions in the 1960s and 1970s. Another introduction from central Africa to southern/central Europe seems to have occurred, and where these two introductions meet, one recombination event was detected in central Europe. In addition, another recombinant strain was found in central Africa, where the most divergent SINV-I strains also originated. IMPORTANCE This study shows that only a single introduction of SINV into a new geographical area is required for spread and establishment, provided that the requisite vector(s) and reservoir(s) of epizootological and epidemiological importance are present. Furthermore, we present the first report of recombination between two strains of SINV in nature. Our study increases the knowledge on new introductions and dispersal of arboviruses in general and of SINV in particular.
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| 18. |
- Masika, Moses Muia, et al.
(författare)
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Serological Evidence of Exposure to Onyong-Nyong and Chikungunya Viruses in Febrile Patients of Rural Taita-Taveta County and Urban Kibera Informal Settlement in Nairobi, Kenya
- 2022
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Ingår i: Viruses. - : MDPI. - 1999-4915. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- Several alphaviruses, such as chikungunya (CHIKV) and Onyong-nyong (ONNV), are endemic in Kenya and often cause outbreaks in different parts of the country. We assessed the seroprevalence of alphaviruses in patients with acute febrile illness in two geographically distant areas in Kenya with no previous record of alphavirus outbreaks. Blood samples were collected from febrile patients in health facilities located in the rural Taita-Taveta County in 2016 and urban Kibera informal settlement in Nairobi in 2017 and tested for CHIKV IgG and IgM antibodies using an in-house immunofluorescence assay (IFA) and a commercial ELISA test, respectively. A subset of CHIKV IgG or IgM antibody-positive samples were further analyzed using plaque reduction neutralization tests (PRNT) for CHIKV, ONNV, and Sindbis virus. Out of 537 patients, 4 (0.7%) and 28 (5.2%) had alphavirus IgM and IgG antibodies, respectively, confirmed on PRNT. We show evidence of previous and current exposure to alphaviruses based on serological testing in areas with no recorded history of outbreaks.
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| 19. |
- Mittler, Eva, et al.
(författare)
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Human antibody recognizing a quaternary epitope in the Puumala virus glycoprotein provides broad protection against orthohantaviruses
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:636
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Tidskriftsartikel (refereegranskat)abstract
- The rodent-borne hantavirus Puumala virus (PUUV) and related agents cause hemorrhagic fever with renal syndrome (HFRS) in humans. Other hantaviruses, including Andes virus (ANDV) and Sin Nombre virus, cause a distinct zoonotic disease, hantavirus cardiopulmonary syndrome (HCPS). Although these infections are severe and have substantial case fatality rates, no FDA-approved hantavirus countermeasures are available. Recent work suggests that monoclonal antibodies may have therapeutic utility. We describe here the isolation of human neutralizing antibodies (nAbs) against tetrameric Gn/Gc glycoprotein spikes from PUUV-experienced donors. We define a dominant class of nAbs recognizing the "capping loop" of Gn that masks the hydrophobic fusion loops in Gc. A subset of nAbs in this class, including ADI-42898, bound Gn/Gc complexes but not Gn alone, strongly suggesting that they recognize a quaternary epitope encompassing both Gn and Gc. ADI-42898 blocked the cell entry of seven HCPS- and HFRS-associated hantaviruses, and single doses of this nAb could protect Syrian hamsters and bank voles challenged with the highly virulent HCPS-causing ANDV and HFRS-causing PUUV, respectively. ADI-42898 is a promising candidate for clinical development as a countermeasure for both HCPS and HFRS, and its mode of Gn/Gc recognition informs the development of broadly protective hantavirus vaccines.
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| 20. |
- Paulsen, Katrine M., et al.
(författare)
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High-throughput sequencing of two European strains of tick-borne encephalitis virus (TBEV), Hochosterwitz and 1993/783
- 2021
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Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis virus (TBEV) is a medically important arbovirus, widespread in Europe and Asia. The virus is primarily transmitted to humans and animals by bites from ticks and, in rare cases, by consumption of unpasteurized dairy products. The aim of this study was to sequence and characterize two TBEV strains with amplicon sequencing by designing overlapping primers. The amplicon sequencing, via Illumina MiSeq, covering nearly the entire TBEV genome, was successful: We retrieved and characterized the complete polyprotein sequence of two TBEV strains, Hochosterwitz and 1993/783 from Austria and Sweden, respectively. In this study the previous phylogenetic analysis of both strains was confirmed to be of the European subtypes of TBEV (TBEV-Eu) by whole genome sequencing. The Hochosterwitz strain clustered with the two strains KrM 93 and KrM 213 from South Korea, and the 1993/783 strain clustered together with the NL/UH strain from the Netherlands. Our study confirms the suitability and rapidness of the high-throughput sequencing method used to produce complete TBEV genomes from TBEV samples of high viral load giving high-molecular-weight cDNA with large overlapping amplicons.
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| 21. |
- Plyusnin, Alexander, et al.
(författare)
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Validation of an antigenic site targeted by monoclonal antibodies against Puumala virus
- 2023
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Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 104:10
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Tidskriftsartikel (refereegranskat)abstract
- Identification of B-cell epitopes facilitates the development of vaccines, therapeutic antibodies and diagnostic tools. Previously, the binding site of the bank vole monoclonal antibody (mAb) 4G2 against Puumala virus (PUUV, an orthohantavirus in the Hantaviridae family of the Bunyavirales order) was predicted using a combination of methods, including pepscan, phage-display, and site-directed mutagenesis of vesicular stomatitis virus (VSV) particles pseudotyped with Gn and Gc glycoproteins from PUUV. These techniques led to the identification of the neutralization escape mutation F915A. To our surprise, a recent crystal structure of PUUV Gc in complex with Fab 4G2 revealed that residue F915 is distal from epitope of mAb 4G2. To clarify this issue and explore potential explanations for the inconsistency, we designed a mutagenesis experiment to probe the 4G2 epitope, with three PUUV pseudoviruses carrying amino acid changes E725A, S944F, and S946F, located within the structure-based 4G2 epitope on the Gc. These amino acid changes were able to convey neutralization escape from 4G2, and S944F and S946F also conveyed escape from neutralization by human mAb 1C9. Furthermore, our mapping of all the known neutralization evasion sites from hantaviral Gcs onto PUUV Gc revealed that over 60 % of these sites reside within or close to the epitope of mAb 4G2, indicating that this region may represent a crucial area targeted by neutralizing antibodies against PUUV, and to a lesser extent, other hantaviruses. The identification of this site of vulnerability could guide the creation of subunit vaccines against PUUV and other hantaviruses in the future.
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| 22. |
- Rissanen, Ilona, et al.
(författare)
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Molecular rationale for antibody-mediated targeting of the hantavirus fusion glycoprotein
- 2020
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Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The intricate lattice of Gn and Gc glycoprotein spike complexes on the hantavirus envelope facilitates host-cell entry and is the primary target of the neutralizing antibody-mediated immune response. Through study of a neutralizing monoclonal antibody termed mAb P-4G2, which neutralizes the zoonotic pathogen Puumala virus (PUUV), we provide a molecular-level basis for antibody-mediated targeting of the hantaviral glycoprotein lattice. Crystallographic analysis demonstrates that P-4G2 binds to a multi-domain site on PUUV Gc and may preclude fusogenic rearrangements of the glycoprotein that are required for host-cell entry. Furthermore, cryoelectron microscopy of PUUV-like particles in the presence of P-4G2 reveals a lattice-independent configuration of the Gc, demonstrating that P-4G2 perturbs the (Gn-Gc)(4) lattice. This work provides a structure-based blueprint for rationalizing antibody-mediated targeting of hantaviruses.
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| 23. |
- Rönnberg, Bengt, et al.
(författare)
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Compensating for cross-reactions using avidity and computation in a suspension multiplex immunoassay for serotyping of Zika versus other flavivirus infections
- 2017
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Ingår i: Medical Microbiology and Immmunology. - : SPRINGER. - 0300-8584 .- 1432-1831. ; 206:5, s. 383-401
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Tidskriftsartikel (refereegranskat)abstract
- The recent spread of Zika virus (ZIKV) in the Americas and Asia necessitates an increased preparedness for improved maternal and perinatal health and blood safety. However, serological cross-reactions, especially to Dengue virus (DENV), complicate ZIKV antibody serodiagnosis. A novel "pan-Flavi" suspension multiplex immunoassay (PFSMIA) using 25 antigens, whole virus (WV), non-structural protein 1 (NS1), and envelope (E) proteins, from 7 zoonotic flaviviruses for specific detection of ZIKV and DENV IgM and IgG was developed. Patterns of antibody cross-reactivity, avidity, and kinetics were established in 104 sera from returning travelers with known ZIKV and DENV infections. PFSMIA gave IgM- and IgG-sensitivities for both viruses of 96-100%, compared to an immunofluorescence assay. Main IgM cross-reactions were to NS1, for IgG to the E and WV antigens. Infecting virus yielded reactivity to several antigens of the homologous virus, while cross-reactions tended to occur only to a single antigen from heterologous virus(es). A specificity-enhancing computer procedure took into account antibody isotype, number of antibody-reactive antigens per virus, avidity, average degree of cross-reactivity to heterologous flavivirus antigens, and reactivity changes in serial sera. It classified all 50 cases correctly. Applied to sera from 200 pregnant women and 173 blood donors from Sweden, one blood donor was found ZIKV NS1 IgM positive, and another as ZIKV NS1 IgG positive. These samples did not react with other ZIKV antigens and were thereby judged as false-positives. PFSMIA provided sensitive and specific ZIKV and DENV serology, warranting high-throughput serological surveillance and a minimized need for laborious and expensive virus neutralization assays.
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| 24. |
- Shakya, Ruchika, et al.
(författare)
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Inkoo and Sindbis viruses in blood sucking insects, and a serological study for Inkoo virus in semi-domesticated Eurasian tundra reindeer in Norway
- 2022
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Ingår i: Virology Journal. - : Springer Nature. - 1743-422X. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mosquito-borne viruses pose a serious threat to humans worldwide. There has been an upsurge in the number of mosquito-borne viruses in Europe, mostly belonging to the families Togaviridae, genus Alphavirus (Sindbis, Chikungunya), Flaviviridae (West Nile, Usutu, Dengue), and Peribunyaviridae, genus Orthobunyavirus, California serogroup (Inkoo, Batai, Tahyna). The principal focus of this study was Inkoo (INKV) and Sindbis (SINV) virus circulating in Norway, Sweden, Finland, and some parts of Russia. These viruses are associated with morbidity in humans. However, there is a knowledge gap regarding reservoirs and transmission. Therefore, we aimed to determine the prevalence of INKV and SINV in blood sucking insects and seroprevalence for INKV in semi-domesticated Eurasian tundra reindeer (Rangifer tarandus tarandus) in Norway. Materials and methods: In total, 213 pools containing about 25 blood sucking insects (BSI) each and 480 reindeer sera were collected in eight Norwegian reindeer summer pasture districts during 2013–2015. The pools were analysed by RT-PCR to detect INKV and by RT-real-time PCR for SINV. Reindeer sera were analysed for INKV-specific IgG by an Indirect Immunofluorescence Assay (n = 480, IIFA) and a Plaque Reduction Neutralization Test (n = 60, PRNT). Results: Aedes spp. were the most dominant species among the collected BSI. Two of the pools were positive for INKV-RNA by RT-PCR and were confirmed by pyrosequencing. The overall estimated pool prevalence (EPP) of INKV in Norway was 0.04%. None of the analysed pools were positive for SINV. Overall IgG seroprevalence in reindeer was 62% positive for INKV by IIFA. Of the 60 reindeer sera- analysed by PRNT for INKV, 80% were confirmed positive, and there was no cross-reactivity with the closely related Tahyna virus (TAHV) and Snowshoe hare virus (SSHV). Conclusion: The occurrence and prevalence of INKV in BSI and the high seroprevalence against the virus among semi-domesticated reindeer in Norway indicate that further studies are required for monitoring this virus. SINV was not detected in the BSI in this study, however, human cases of SINV infection are yearly reported from other regions such as Rjukan in south-central Norway. It is therefore essential to monitor both viruses in the human population. Our findings are important to raise awareness regarding the geographical distribution of these mosquito-borne viruses in Northern Europe.
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| 25. |
- Tonteri, Elina, et al.
(författare)
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The Three Subtypes of Tick-Borne Encephalitis Virus Induce Encephalitis in a Natural Host, the Bank Vole (Myodes glareolus)
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e81214-
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis virus (TBEV) infects bank voles (Myodes glareolus) in nature, but the relevance of rodents for TBEV transmission and maintenance is unclear. We infected colonized bank voles subcutaneously to study and compare the infection kinetics, acute infection, and potential viral persistence of the three known TBEV subtypes: European (TBEV-Eur), Siberian (TBEV-Sib) and Far Eastern (TBEV-FE). All strains representing the three subtypes were infective and highly neurotropic. They induced (meningo) encephalitis in some of the animals, however most of the cases did not present with apparent clinical symptoms. TBEV-RNA was cleared significantly slower from the brain as compared to other organs studied. Supporting our earlier findings in natural rodent populations, TBEV-RNA could be detected in the brain for up to 168 days post infection, but we could not demonstrate infectivity by cell culture isolation. Throughout all time points post infection, RNA of the TBEV-FE was detected significantly more often than RNA of the other two strains in all organs studied. TBEV-FE also induced prolonged viremia, indicating distinctive kinetics in rodents in comparison to the other two subtypes. This study shows that bank voles can develop a neuroinvasive TBEV infection with persistence of viral RNA in brain, and mount an anti-TBEV IgG response. The findings also provide further evidence that bank voles can serve as sentinels for TBEV endemicity.
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