| 1. |
- Zell, R., et al.
(författare)
-
ICTV Virus Taxonomy Profile : Picornaviridae
- 2017
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 98:10, s. 2421-2422
-
Tidskriftsartikel (refereegranskat)abstract
- The family Picornaviridae comprises small non-enveloped viruses with RNA genomes of 6.7 to 10.1 kb, and contains > 30 genera and > 75 species. Most of the known picornaviruses infect mammals and birds, but some have also been detected in reptiles, amphibians and fish. Many picornaviruses are important human and veterinary pathogens and may cause diseases of the central nervous system, heart, liver, skin, gastrointestinal tract or upper respiratory tract. Most picornaviruses are transmitted by the faecal-oral or respiratory routes. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Picornaviridae, which is available at www. ictv. global/report/picornaviridae.
|
|
| 2. |
- Knowles, N J, et al.
(författare)
-
Family - Picornaviridae
- 2012
-
Ingår i: Virus Taxonomy. - San Diego - London : Elsevier. - 9780123846846 ; , s. 855-881
-
Bokkapitel (refereegranskat)abstract
- This chapter focuses on Picornaviridae family whose member genuses includeEnterovirus, Cardiovirus, Aphthovirus, Hepatovirus, and Parechovirus. The virions of this family consist of a capsid with no envelope and surrounds a core of ssRNA. Hydrated native particles are 30 nm in diameter, but vary from 22 to 30 nm in electron micrographs due to drying and flattening during preparation. The virions contain one molecule of positive sense, ssRNA, and possess a single long ORF. The UTRs at both termini contain regions of secondary structure, which are essential to genome function. In addition to the major CPs, 1A, 1B, 1C and 1D, and 3B (VPg), small amounts of 1AB (VP0) are commonly seen in lieu of one or more copies of 1A and 1B. Protein 1A is small in hepatoviruses, and 1AB is uncleaved in avihepatoviruses, kobuviruses, parechoviruses, and a number of unclassified picornaviruses. Some picornaviruses carry a sphingosine-like molecule in a cavity located inside 1D, and protein 1A generally has a molecule of myristic acid covalently attached to the amino terminal glycine. The virion RNA is infectious and serves as both the genome and the viral mRNA. Infection is generally cytolytic, but persistent infections are common with some species and reported with others. Poliovirus infected cells undergo extensive vacuolation as membranes are reorganized into viral replication complexes.
|
|
| 3. |
|
|
| 4. |
- Murphy, Rachel A, et al.
(författare)
-
Omega-3 and omega-6 polyunsaturated fatty acid biomarkers and sleep : a pooled analysis of cohort studies On behalf of the Fatty Acids and Outcomes Research Consortium (FORCE).
- 2022
-
Ingår i: American Journal of Clinical Nutrition. - : Oxford University Press (OUP). - 0002-9165 .- 1938-3207. ; 115:3, s. 864-876
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: n-3 and n-6 polyunsaturated fatty acids (PUFAs) have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters.OBJECTIVES: To assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium.METHODS: Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts. Participants were between 35 to 96 years old and from 5 nations. Circulating measures included alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), EPA + DPA + DHA, linoleic acid and arachidonic acid. Sleep duration (10 cohorts, N = 18,791) was categorized as short (≤6 hours), 7-8 hours (reference) or long (9 + hours). Difficulty falling sleeping (8 cohorts, N = 12,500) was categorized as yes or no. Associations between PUFAs, sleep duration, and difficulty falling sleeping were assessed by cross-sectional multinomial logistic regression using standardized protocols and covariates. Cohort-specific multivariable-adjusted odds ratios (ORs) per quintile of PUFAs were pooled with inverse-variance weighted meta-analysis.RESULTS: In pooled analysis adjusted for sociodemographics and health status, participants with higher very long-chain n-3 PUFAs were less likely to have long sleep duration. Comparing top vs. bottom quintiles, the multivariable-adjusted OR (95% confidence interval, CI) for long-sleep was 0.78 (0.65, 0.95) for DHA and for EPA + DPA + DHA, 0.76 (0.63, 0.93). Significant associations were not identified for ALA and n-6 PUFA with short sleep duration, or difficulty falling sleeping.CONCLUSIONS: Participants with higher levels of very long-chain n-3 PUFAs were less likely to have long sleep duration. While objective biomarkers reduce recall bias and misclassification, the cross-sectional design limits assessment of the temporal nature of this relationship. These novel findings across 12 cohorts highlight the need for experimental and biological assessments of very long-chain n-3 PUFAs and sleep duration.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Simmonds, P., et al.
(författare)
-
Recommendations for the nomenclature of enteroviruses and rhinoviruses
- 2020
-
Ingår i: Archives of Virology. - : Springer. - 0304-8608 .- 1432-8798. ; 165, s. 793-797
-
Tidskriftsartikel (refereegranskat)abstract
- Enteroviruses (EVs) and rhinoviruses (RVs) are significant pathogens of humans and are the subject of intensive clinical and epidemiological research and public health measures, notably in the eradication of poliovirus and in the investigation and control of emerging pathogenic EV types worldwide. EVs and RVs are highly diverse in their antigenic properties, tissue tropism, disease associations and evolutionary relationships, but the latter often conflict with previously developed biologically defined terms, such as "coxsackieviruses", "polioviruses" and "echoviruses", which were used before their genetic interrelationships were understood. This has created widespread formatting problems and inconsistencies in the nomenclature for EV and RV types and species in the literature and public databases. As members of the International Committee for Taxonomy of Viruses (ICTV) Picornaviridae Study Group, we describe the correct use of taxon names for these viruses and have produced a series of recommendations for the nomenclature of EV and RV types and their abbreviations. We believe their adoption will promote greater clarity and consistency in the terminology used in the scientific and medical literature. The recommendations will additionally provide a useful reference guide for journals, other publications and public databases seeking to use standardised terms for the growing multitude of enteroviruses and rhinoviruses described worldwide.
|
|
| 8. |
- Beyder, Arthur, et al.
(författare)
-
Loss-of-Function of the Voltage-Gated Sodium Channel Na(V)1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome
- 2014
-
Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7, s. 1659-1668
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: SCN5A encodes the a-subunit of the voltage-gated sodium channel Na(V)1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Na(V)1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted Na(V)1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-Na(V)1.5 had the greatest effect in reducing Na(V)1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS. CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt Na(V)1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
|
|
| 9. |
- Beyder, Arthur, et al.
(författare)
-
Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome.
- 2014
-
Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 146:7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of NaV1.5.METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without IBS (controls). Mutant forms of SCN5A were expressed in human embryonic kidney-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls.RESULTS: Missense mutations were found in SCN5A in 13 of 584 patients (2.2%, probands). Diarrhea-predominant IBS was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (31%) than diarrhea-predominant IBS (10%; P < .05). Electrophysiologic analysis showed that 10 of 13 detected mutations disrupted NaV1.5 function (9 loss-of-function and 1 gain-of-function function). The p. A997T-NaV1.5 had the greatest effect in reducing NaV1.5 function. Incubation of cells that expressed this variant with mexiletine restored their sodium current and administration of mexiletine to 1 carrier of this mutation (who had constipation-predominant IBS) normalized their bowel habits. In the genome-wide association study and 4 replicated studies, the SCN5A locus was strongly associated with IBS.CONCLUSIONS: About 2% of patients with IBS carry mutations in SCN5A. Most of these are loss-of-function mutations that disrupt NaV1.5 channel function. These findings provide a new pathogenic mechanism for IBS and possible treatment options.
|
|
| 10. |
|
|
| 11. |
- Engert, Andreas, et al.
(författare)
-
The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
-
Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
-
Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
|
|
| 12. |
- Ezzat, Kariem, et al.
(författare)
-
PepFect 14, a novel cell-penetrating peptide for oligonucleotide delivery in solution and as solid formulation
- 2011
-
Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 39:12, s. 5284-5298
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous human genetic diseases are caused by mutations that give rise to aberrant alternative splicing. Recently, several of these debilitating disorders have been shown to be amenable for splice-correcting oligonucleotides (SCOs) that modify splicing patterns and restore the phenotype in experimental models. However, translational approaches are required to transform SCOs into usable drug products. In this study, we present a new cell-penetrating peptide, PepFect14 (PF14), which efficiently delivers SCOs to different cell models including HeLa pLuc705 and mdx mouse myotubes; a cell culture model of Duchenne's muscular dystrophy (DMD). Non-covalent PF14-SCO nanocomplexes induce splice-correction at rates higher than the commercially available lipid-based vector Lipofectamine™ 2000 (LF2000) and remain active in the presence of serum. Furthermore, we demonstrate the feasibility of incorporating this delivery system into solid formulations that could be suitable for several therapeutic applications. Solid dispersion technique is utilized and the formed solid formulations are as active as the freshly prepared nanocomplexes in solution even when stored at an elevated temperatures for several weeks. In contrast, LF2000 drastically loses activity after being subjected to same procedure. This shows that using PF14 is a very promising translational approach for the delivery of SCOs in different pharmaceutical forms.
|
|
| 13. |
- Kirdok, Emrah, et al.
(författare)
-
Metagenomic analysis of Mesolithic chewed pitch reveals poor oral health among stone age individuals
- 2024
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Prehistoric chewed pitch has proven to be a useful source of ancient DNA, both from humans and their microbiomes. Here we present the metagenomic analysis of three pieces of chewed pitch from Huseby Klev, Sweden, that were dated to 9,890-9,540 before present. The metagenomic profile exposes a Mesolithic oral microbiome that includes opportunistic oral pathogens. We compared the data with healthy and dysbiotic microbiome datasets and we identified increased abundance of periodontitis-associated microbes. In addition, trained machine learning models predicted dysbiosis with 70-80% probability. Moreover, we identified DNA sequences from eukaryotic species such as red fox, hazelnut, red deer and apple. Our results indicate a case of poor oral health during the Scandinavian Mesolithic, and show that pitch pieces have the potential to provide information on material use, diet and oral health.
|
|
| 14. |
- Leta, Tesfaye H., et al.
(författare)
-
The use of antibiotic-loaded bone cement and systemic antibiotic prophylactic use in 2,971,357 primary total knee arthroplasties from 2010 to 2020: an international register-based observational study among countries in Africa, Europe, North America, and Oceania
- 2023
-
Ingår i: Acta Orthopaedica. - 1745-3674 .- 1745-3682. ; 94, s. 416-425
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose — Antibiotic-loaded bone cement (ALBC) and systemic antibiotic prophylaxis (SAP) have been used to reduce periprosthetic joint infection (PJI) rates. We investigated the use of ALBC and SAP in primary total knee arthroplasty (TKA). Patients and methods — This observational study is based on 2,971,357 primary TKAs reported in 2010–2020 to national/regional joint arthroplasty registries in Australia, Den-mark, Finland, Germany, Italy, the Netherlands, New Zealand, Norway, Romania, South Africa, Sweden, Switzerland, the UK, and the USA. Aggregate-level data on trends and types of bone cement, antibiotic agents, and doses and duration of SAP used was extracted from participating registries. Results — ALBC was used in 77% of the TKAs with variation ranging from 100% in Norway to 31% in the USA. Palacos R+G was the most common (62%) ALBC type used. The primary antibiotic used in ALBC was gentamicin (94%). Use of ALBC in combination with SAP was common practice (77%). Cefazolin was the most common (32%) SAP agent. The doses and duration of SAP used varied from one single preoperative dosage as standard practice in Bolzano, Italy (98%) to 1-day 4 doses in Norway (83% of the 40,709 TKAs reported to the Norwegian arthroplasty register). Conclusion — The proportion of ALBC usage in primary TKA varies internationally, with gentamicin being the most common antibiotic. ALBC in combination with SAP was common practice, with cefazolin the most common SAP agent. The type of ALBC and type, dose, and duration of SAP varied among participating countries.
|
|
| 15. |
|
|
| 16. |
- Nix, W Allan, et al.
(författare)
-
Detection of all known parechoviruses by real-time PCR.
- 2008
-
Ingår i: Journal of clinical microbiology. - 1098-660X. ; 46:8, s. 2519-24
-
Tidskriftsartikel (refereegranskat)abstract
- The Parechovirus genus of the Picornaviridae family contains two species, Human parechovirus (HPeV) and Ljungan virus (LV). The HPeVs (including the former echoviruses 22 and 23, now HPeV type 1 (HPeV1) and HPeV2, respectively) cause a wide spectrum of disease, including aseptic meningitis, gastroenteritis, encephalitis, acute respiratory illness, and neonatal sepsis-like disease. The LVs were isolated from bank voles in Sweden during a search for an infectious agent linked to fatal myocarditis cases in humans. Because of the decline in use of cell culture and neutralization to investigate enterovirus-like disease, very few laboratories currently have the capability to test for parechoviruses. We have developed a real-time reverse transcription-PCR (RT-PCR) assay for detection of all known members of the genus Parechovirus. The assay targets the conserved regions in the 5' nontranslated region (5'NTR) of the parechovirus genome and can detect both HPeVs and LVs, unlike other published parechovirus 5' NTR assays, which only detect known HPeVs or only LVs. HPeV and LV can be differentiated by sequencing the 5'NTR real-time RT-PCR amplicon, when needed. The assay is approximately 100 times more sensitive than cell culture and may be used to test original clinical specimens. The availability of a broad-specificity PCR method should facilitate the detection of new human parechoviruses, as well as new parechoviruses in other mammalian species, and provide an opportunity to investigate the role of these viruses in human and animal disease.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Alksnis, M., et al.
(författare)
-
Use of synthetic oligodeoxyribonucleotides for type-specific identification of coxsackie B viruses
- 1989
-
Ingår i: Molecular and Cellular Probes. - : Elsevier BV. - 0890-8508 .- 1096-1194. ; 3:2, s. 103-108
-
Tidskriftsartikel (refereegranskat)abstract
- Synthetic oligodeoxyribonucleotides were used for type-specific identification of members of the coxsackie B virus group by nucleic acid hybridization. Two pairs of oligonucleotide chains were constructed based on nucleotide sequences in the VP1 regions of coxsackieviruses B3 and B4. Each labelled probe had a length of 24 nucleotides. The results showed that the oligonucleotide hybridized in a type-specific manner when assayed with extracts from cells infected with all different coxsackie B viruses. A method based on similar principles may thus be used for enterovirus typing.
|
|
| 21. |
|
|
| 22. |
- Au, Gough G, et al.
(författare)
-
Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21.
- 2005
-
Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 26:6, s. 1471-6
-
Tidskriftsartikel (refereegranskat)abstract
- Cultured melanoma cell lines despite exhibiting similar in vitro morphology, display significant phenotypic and growth rate differences when propagated as in vivo xenografts. Previously we have shown that Coxsackievirus A21 (CVA21) lytically infects in vitro cultures of malignant melanoma cells and is efficient at reducing the tumor burden of mice bearing slow-growing SK-Mel-28 melanoma xenografts. The oncolytic activity of CVA21 against in vivo melanoma xenografts, which possess rapid growth rates and more extensive vascular structure than SK-Mel-28 xenografts warrants further investigation. In the present study we evaluated the oncolytic action of CVA21 against rapidly growing melanoma xenografts (ME4405) which exhibit a highly vascular phenotype. Flow cytometric analysis indicated that in vitro cultures of ME4405 cells expressed comparable levels of the CVA21 cellular receptors, ICAM-1 (intercellular adhesion molecules-1) and DAF (decay accelerating factor) to SK-Mel-28 cells. Despite similar levels of CVA21 receptor expression, SK-Mel-28 cells appear to be more susceptible to viral lysis than ME4405 cells, even though the kinetics of virus replication in both lines was comparable. Intratumoral, intraperitoneal or intravenous administration of CVA21 were equally effective in reducing the tumor volume of ME4405 xenografts in immunodeficient mice, and provides further evidence for the use of CVA21 as a novel oncolytic agent against varying phenotypes of malignant melanoma.
|
|
| 23. |
- Ceder, Mikaela M., et al.
(författare)
-
The Fly Homologue of MFSD11 Is Possibly Linked to Nutrient Homeostasis and Has a Potential Role in Locomotion : A First Characterization of the Atypical Solute Carrier CG18549 in Drosophila Melanogaster
- 2021
-
Ingår i: Insects. - : MDPI. - 2075-4450. ; 12:11
-
Tidskriftsartikel (refereegranskat)abstract
- Cellular transport and function are dependent on substrate influx and efflux of various compounds. In humans, the largest superfamily of transporters is the SoLute Carriers (SLCs). Many transporters are orphans and little to nothing is known about their expression and/or function, yet they have been assigned to a cluster called atypical SLCs. One of these atypical SLCs is MFSD11. Here we present a first in-depth characterization of the MFSD11, CG18549. By gene expression and behavior analysis on ubiquitous and brain-specific knockdown flies. CG18549 knockdown flies were found to have altered adipokinetic hormone and adipokinteic hormone receptor expression as well as reduced vesicular monoamine transporter expression; to exhibit an altered locomotor behavior, and to have an altered reaction to stress stimuli. Furthermore, the gene expression of CG18549 in the brain was visualized and abundant expression in both the larvae and adult brain was observed, a result that is coherent with the FlyAtlas Anatomy microarray. The exact mechanism behind the observed behaviors is not fully understood, but this study provides new insights into the expression and function of CG18549. Clearly, these results provide a strong example as to why it is vital to fully characterize orphan transporters and through that gain knowledge about the body during normal condition and disease.
|
|
| 24. |
|
|
| 25. |
- Ekström, Jens-Ola, et al.
(författare)
-
Replication of Ljungan virus in cell culture : the genomic 5'-end, infectious cDNA clones and host cell response to viral infections
- 2007
-
Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 130:1-2, s. 129-139
-
Tidskriftsartikel (refereegranskat)abstract
- Ljungan virus (LV) is a picornavirus recently isolated from bank voles (Clethrionomys glareolus). The previously uncharacterised 5'-end sequence of the LV genome was determined. Infectious cDNA clones were constructed of the wild type LV prototype strain 87-012 and of the cytolytically replicating cell culture adapted variant 87-012G. Virus generated from cDNA clones showed identical growth characteristics as uncloned virus stocks. Cell culture adapted LV, 87-012G, showed a clear cytopathic effect (CPE) at 3-4 days post-infection (p.i.). Virus titers, determined by plaque titration, increased however only within the first 18h p.i. Replication of LV (+) strand RNA was determined by real-time PCR and corresponded in time with increasing titers. In contrast, the amounts of the replication intermediate, the (-) strand, continued to increase until the cells showed CPE. This indicates separate controlling mechanisms for replication of LV (+) and (-) genome strands. Replication was also monitored by immunofluorescence (IF) staining. IF staining of both prototype 87-012 and the CPE causing 87-012G showed groups of 5-25 infected cells at 48h p.i., suggesting a, for picornaviruses, not previously described direct cell-to-cell transmission.
|
|
| 26. |
- EL Hiar, Raida, et al.
(författare)
-
Enteroviral Central Nervous System Infections in Children of the Region of Monastir, Tunisia : Diagnosis, Laboratory Findings of Cerebrospinal Fluid and Clinical Manifestations
- 2012
-
Ingår i: Indian Journal of Virology. - : Springer Science and Business Media LLC. - 0970-2822 .- 0974-0120. ; 23:3, s. 294-302
-
Tidskriftsartikel (refereegranskat)abstract
- Human enteroviruses (HEV) are one of the major causes of central nervous system (CNS) infections in pediatrics. A prospective study was conducted to assess the epidemiological, clinical, and laboratory characteristics of enterovirus (EV) infections of the CNS in children under 15-years-old, suspected of having viral CNS infections and admitted to the Pediatric Department of Monastir University Hospital, Tunisia. Enteroviral RNA was detected by 5' NCR nested RT-PCR assay in 33 % (20 out of 60) of cerebrospinal fluid specimens, whereas only six samples (10 %) were EV positive in cell culture. EV-positive patients were clustered according to their clinical manifestations, predominantly diagnosed as aseptic meningitis (65 %) and meningoencephalitis (20 %). Fever, headache, vomiting, and neck stiffness were the most pronounced symptoms. Pleocytosis with the predominance of lymphocytes was observed in 60 % of EV positive specimens. Although patients suffering from EV infections were encountered throughout the year, most occurred during spring and summer months. Using VP1-2A nested RT-PCR and sequence analysis, three of the 20 positive HEV were identified as Echovirus (E)-9. This is the first report of a cluster of aseptic meningitis cases caused by E-9 in Monastir.
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
- Gullberg, Maria, et al.
(författare)
-
A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.
- 2010
-
Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 84:12, s. 5868-5879
-
Tidskriftsartikel (refereegranskat)abstract
- Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.
|
|
| 30. |
- Gullberg, Maria, et al.
(författare)
-
Characterization of a putative ancestor of coxsackievirus B5.
- 2010
-
Ingår i: Journal of Virology. - 0022-538X .- 1098-5514. ; 84, s. 9695-9708
-
Tidskriftsartikel (refereegranskat)abstract
- Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major co-circulating lineages. Ancestral capsid sequences were inferred from sequences of these contemporary CVB5 isolates using maximum likelihood methods. By using Bayesian phylodynamic analysis, the inferred VP1 ancestral sequence was dated back to 1854 (1807-1898). In order to study the properties of the putative ancestral capsid, the entire ancestral P1 sequence was synthesized de novo and inserted into the replicative backbone of an infectious CVB5 cDNA clone. Characterization of the recombinant virus in cell culture showed that fully functional infectious virus particles were assembled and that these viruses displayed properties similar to those of modern isolates, in terms of receptor preferences, plaque phenotype, growth characteristics and cell tropism. This is the first report describing resurrection and characterization of a picornavirus with a putative ancestral capsid. Our approach, including phylogenetics-based reconstruction of viral predecessors, could serve as a starting point for experimental studies of viral evolution and might also provide an alternative strategy in the development of vaccines.
|
|
| 31. |
|
|
| 32. |
- Hall, Michael, et al.
(författare)
-
Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria
- 2016
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:51, s. 14733-14738
-
Tidskriftsartikel (refereegranskat)abstract
- Infection by the human bacterial pathogen Listeria monocytogenes is mainly controlled by the positive regulatory factor A (PrfA), a member of the Crp/Fnr family of transcriptional activators. Published data suggest that PrfA requires the binding of a cofactor for full activity, and it was recently proposed that glutathione (GSH) could fulfill this function. Here we report the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif. These structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell. The crystal structure of PrfAWT in complex only with DNA confirms that PrfAWT can adopt a DNA binding-compatible structure without binding the GSH activator molecule. By binding to PrfA in the cytosol of the host cell, GSH induces the correct fold of the HTH motifs, thus priming the PrfA protein for DNA interaction.
|
|
| 33. |
- Israelsson, Stina, et al.
(författare)
-
Cytolytic replication of echoviruses in colon cancer cell lines
- 2011
-
Ingår i: Virology Journal. - 1743-422X. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Colorectal cancer is one of the most common cancers in the world, killing nearly 50% of patients afflicted. Though progress is being made within surgery and other complementary treatments, there is still need for new and more effective treatments. Oncolytic virotherapy, meaning that a cancer is cured by viral infection, is a promising field for finding new and improved treatments. We have investigated the oncolytic potential of several low-pathogenic echoviruses with rare clinical occurrence. Echoviruses are members of the enterovirus genus within the family Picornaviridae.METHODS: Six colon cancer cell lines (CaCo-2, HT29, LoVo, SW480, SW620 and T84) were infected by the human enterovirus B species echovirus 12, 15, 17, 26 and 29, and cytopathic effects as well as viral replication efficacy were investigated. Infectivity was also tested in spheroids grown from HT29 cells.RESULTS: Echovirus 12, 17, 26 and 29 replicated efficiently in almost all cell lines and were considered highly cytolytic. The infectivity of these four viruses was further evaluated in artificial tumors (spheroids), where it was found that echovirus 12, 17 and 26 easily infected the spheroids.CONCLUSIONS: We have found that echovirus 12, 17 and 26 have potential as oncolytic agents against colon cancer, by comparing the cytolytic capacity of five low-pathogenic echoviruses in six colon cancer cell lines and in artificial tumors.
|
|
| 34. |
- Israelsson, Stina, et al.
(författare)
-
Improved replication efficiency of echovirus 5 after transfection of colon cancer cells using an authentic 5' RNA genome end methodology
- 2014
-
Ingår i: Investigational new drugs. - : Springer Science and Business Media LLC. - 0167-6997 .- 1573-0646. ; 32:6, s. 1063-1070
-
Tidskriftsartikel (refereegranskat)abstract
- Oncolytic virotherapy is a promising novel form of cancer treatment, but the therapeutic efficiency needs improvement. A potential strategy to enhance the therapeutic effect of oncolytic viruses is to use infectious nucleic acid as therapeutic agent to initiate an oncolytic infection, without administrating infectious viral particles. Here we demonstrate improved viral replication activation efficiency when transfecting cells with 5’ end authentic in vitro transcribed enterovirus RNA as compared to genomic RNA with additional non-genomic 5’ nucleotides generated by conventional cloning methods. We used echovirus 5 (E5) as an oncolytoc model virus due to its ability to replicate in and completely destroy five out of six colon cancer cell lines and kill artificial colon cancer tumors (HT29 spheroids), as shown here. An E5 infectious cDNA clone including a hammerhead ribozyme sequence was used to generate in vitro transcripts with native 5’ genome ends. In HT29 cells, activation of virus replication is approximately 20-fold more efficient for virus genome transcripts with native 5’ genome ends compared to E5 transcripts generated from a standard cDNA clone. This replication advantage remains when viral progeny release starts by cellular lysis 22 h post transfection. Hence, a native 5’ genomic end improves infection activation efficacy of infectious nucleic acid, potentially enhancing its therapeutic effect when used for cancer treatment. The clone design with a hammerhead ribozyme is likely to be applicable to a variety of oncolytic positive sense RNA viruses for the purpose of improving the efficacy of oncolytic virotherapy.
|
|
| 35. |
|
|
| 36. |
- Israelsson, Stina, et al.
(författare)
-
Studies of Echovirus 5 interactions with the cell surface: Heparan sulfate mediates attachment to the host cell.
- 2010
-
Ingår i: Virus Research. - : Elsevier BV. - 0168-1702 .- 1872-7492. ; 151:2, s. 170-176
-
Tidskriftsartikel (refereegranskat)abstract
- Infections caused by Echovirus 5 (E5), an enterovirus of the Picornaviridae family, have been associated with fever, rashes and sporadic cases of aseptic meningitis. To elucidate the receptor usage of this virus, the significance of a previously proposed integrin binding arginine-glycine-aspartic acid (RGD) motif found in the VP3 capsid protein was investigated, as well as the capacity of E5 to interact with heparan sulfate on the cell surface. Using the prototype strain E5 Noyce (E5N), an E5N mutant where the aspartic acid of the RGD motif has been substituted to a glutamic acid and clinical E5 isolates, the RGD motif of VP3 was found to be non-essential and hence not involved in integrin receptor binding. However, E5N and clinical E5 isolates interact with heparan sulfate at the cell surface, as demonstrated by virus replication inhibition assays using heparin and heparinase III, and studies of E5 interactions at the cell surface measured by real-time PCR analysis. In conclusion, E5 utilizes heparan sulfate as a cellular receptor, but the RGD motif of VP3 is not essential for E5 infectivity.
|
|
| 37. |
- Johannesson, Per, et al.
(författare)
-
A novel and rapid method to quantify cytolytic replication of picornaviruses in cell culture
- 2005
-
Ingår i: Journal of virological methods. - : Elsevier BV. - 0166-0934. ; 130, s. 117-123
-
Tidskriftsartikel (refereegranskat)abstract
- Determining viral titers is a key issue in a wide variety of studies regarding different aspects of virology. The standard methods used for determining picornavirus titers are endpoint titration assay and plaque assay, both time consuming and laborious. The method described uses the tetrazolium salt MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide) that is reduced to formazane by cellular dehydrogenase, genes shown to be down-regulated during picornavirus infection. The amount formazane produced correlates with the viral titers obtained and can easily be measured using an ELISA plate reader. The colorimetric method has been evaluated using virus types from different genera of the Picornaviridae family. The MTT method reduces the time spent on determining the viral titers and still maintains a reliable accuracy.
|
|
| 38. |
|
|
| 39. |
- Jonsson, Nina, et al.
(författare)
-
A rapid and efficient method for studies of virus interaction at the host cell surface using enteroviruses and real-time PCR
- 2009
-
Ingår i: Virology Journal. - 1743-422X. ; 6:Article ID: 217
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Measuring virus attachment to host cells is of great importance when trying to identify novel receptors. The presence of a usable receptor is a major determinant of viral host range and cell tropism. Furthermore, identification of appropriate receptors is central for the understanding of viral pathogenesis and gives possibilities to develop antiviral drugs. Attachment is presently measured using radiolabeled and subsequently gradient purified viruses. Traditional methods are expensive and time-consuming and not all viruses are stable during a purification procedure; hence there is room for improvement. Real-time PCR (RT-PCR) has become the standard method to detect and quantify virus infections, including enteroviruses, in clinical samples. For instance, primers directed to the highly conserved 5' untranslated region (5'UTR) of the enterovirus genome enable detection of a wide spectrum of enteroviruses. Here, we evaluate the capacity of the RT-PCR technology to study enterovirus host cell interactions at the cell surface and compare this novel implementation with an established assay using radiolabeled viruses. Results: Both purified and crude viral extracts of CVB5 generated comparable results in attachment studies when analyzed with RT-PCR. In addition, receptor binding studies regarding viruses with coxsackie- nd adenovirus receptor (CAR) and/or decay accelerating factor (DAF) affinity, further demonstrated the possibility to use RT-PCR to measure virus attachment to host cells. Furthermore, the RT-PCR technology and crude viral extracts was used to study attachment with low multiplicity of infection (0.05 x 10(-4)TCID(50)/cell) and low cell numbers (250), which implies the range of potential implementations of the presented technique. Conclusion: We have implemented the well-established RT-PCR technique to measure viral attachment to host cells with high accuracy and reproducibility, at low cost and with less effort than traditional methods. Furthermore, replacing traditional methods with RT-PCR offers the opportunity to use crude virus containing extracts to investigate attachment, which could be considered as a step towards viral attachment studies in a more natural state.
|
|
| 40. |
- Jonsson, Nina, et al.
(författare)
-
Aichi virus infection in elderly people in Sweden.
- 2012
-
Ingår i: Archives of Virology. - : Springer Science and Business Media LLC. - 0304-8608 .- 1432-8798. ; 157:7, s. 1365-1369
-
Tidskriftsartikel (refereegranskat)abstract
- Aichi virus (AiV), genus Kobuvirus, family Picornaviridae, is associated with gastroenteritis in humans. Previous studies have shown high seroprevalence but low incidence (0.9-4.1%) in clinical samples. We report here the first detection of AiV in Sweden. Two hundred twenty-one specimens from hospitalized patients with diarrhea, who were negative for other enteric viruses, were included in the study. AiV were detected in three specimens, all from elderly patients. Phylogenetic analysis revealed that the three Swedish isolates belonged to genotype A and were genetically closest to European and Asian strains of AiV.
|
|
| 41. |
|
|
| 42. |
- Jonsson, Nina, et al.
(författare)
-
Efficient replication of recombinant Enterovirus B types, carrying different P1 genes in the coxsackievirus B5 replicative backbone
- 2015
-
Ingår i: Virus genes. - : Springer Science and Business Media LLC. - 0920-8569 .- 1572-994X. ; 50:3, s. 351-357
-
Tidskriftsartikel (refereegranskat)abstract
- Recombination is an important feature in theevolution of the Enterovirus genus. Phylogenetic studies ofenteroviruses have revealed that the capsid genomic region(P1) is type specific, while the parts of the genome codingfor the non-structural proteins (P2–P3) are species specific.Hence, the genome may be regarded as consisting of twomodules that evolve independently. In this study, it wasinvestigated whether the non-structural coding part of thegenome in one type could support replication of a virus witha P1 region from another type of the same species. A cas-sette vector (pCas) containing a full-length cDNA copy ofcoxsackievirus B5 (CVB5) was used as a replicative back-bone. The P1 region of pCas was replaced with the corre-sponding part from coxsackievirus B3Nancy(CVB3N),coxsackievirus B6Schmitt(CVB6S), and echovirus 7Wal-lace(E7W), all members of theEnterovirus Bspecies. Thereplication efficiency after transfection with clone-derivedin vitro transcribed RNA was studied and compared withthat of pCas. All the recombinant viruses replicated with similar efficiencies and showed threshold cycle (Ct) values,tissue culture infectivity dose 50 %, and plaque-forming unittiters comparable to viruses generated from the pCas con-struct. In addition to this, a clone without the P1 region wasalso constructed, and Western Blot and immunofluorescencestaining analysis showed that the viral genome could betranslated and replicated despite the lack of the structuralprotein-coding region. To conclude, the replicative back-bone of the CVB5 cassette vector supports replication ofintraspecies constructs with P1 regions derived from othermembers of theEnterovirus Bspecies. In addition to this,the replicative backbone can be both translated and repli-cated without the presence of a P1 region.
|
|
| 43. |
- Jonsson, Nina, et al.
(författare)
-
Real-time polymerase chain reaction as a rapid and efficient alternative to estimation of picornavirus titers by tissue culture infectious dose 50% or plaque forming units
- 2009
-
Ingår i: Microbiology and immunology. - : Wiley. - 0385-5600 .- 1348-0421. ; 53:3, s. 149-154
-
Tidskriftsartikel (refereegranskat)abstract
- Quantification of viral infectious units is traditionally measured by methods based on forming plaques in semisolid media (PFU) or endpoint dilution of a virus-containing solution (TCID(50)), methods that are laborious, time-consuming and take on average 3-7 days to carry out. Quantitative real-time PCR is an established method to quantify nucleic acids at high accuracy and reproducibility, routinely used for virus detection and identification. In the present study, a procedure was developed using a two-step real-time PCR and the SYBR Green detection method to study whether there are correlations between TCID(50)/ml, PFU/ml and Ct values generated by real-time PCR enabling rapid and efficient calculation of titer equivalents when working with viruses in the research laboratory. In addition, an external standard with known concentrations was included using in vitro transcribed viral RNA, thus allowing the calculation of the amount of RNA copies needed for various applications (i.e. per plaque or TCID(50)).The results show that there is a correlation between the three quantification methods covering a wide range of concentration of viruses. Furthermore, a general regression line between TCID(50) and Ct values was obtained for all viruses included in the study, which enabled recording titer equivalents using real-time PCR. Finally, by including an external standard, the amount of RNA genomes generating one TCID(50) or PFU for each enterovirus serotype included was determined.
|
|
| 44. |
- Jääskeläinen, Anne J, et al.
(författare)
-
Evidence of ljungan virus specific antibodies in humans and rodents, Finland.
- 2013
-
Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615 .- 1096-9071. ; 85:11, s. 2001-2008
-
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.
|
|
| 45. |
- Karlsson, Beatrice, et al.
(författare)
-
Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection
- 2009
-
Ingår i: Journal of General Virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 90:2, s. 432-441
-
Tidskriftsartikel (refereegranskat)abstract
- In this novel study, we have for the first time identified evolutionarily conserved capsid residues in an individual chronically infected with norovirus (GGII.3). From 2000 to 2003, a total of 147 P1-1 and P2 capsid sequences were sequenced and investigated for evolutionarily conserved and functionally important residues by the evolutionary trace (ET) algorithm. The ET algorithm revealed more absolutely conserved residues (ACR) in the P1-1 domain (47/53, 88 %) as compared with the P2 domain (86/133, 64 %). The capsid P1-1 and P2 domains evolved in time-dependent manner, with a distinct break point observed between autumn/winter of year 2000 (isolates P1, P3 and P5) and spring to autumn of year 2001 (isolates P11, P13 and P15), which presumably coincided with a change of clinical symptoms. Furthermore, the ET analysis revealed a similar receptor-binding pattern as reported for Norwalk and VA387 strains, with the CS-4 and CS-5 patch (Norwalk strain) including residues 329 and 377 and residues 306 and 310, respectively, all being ACR in all partitions. Most interesting was that residues 343, 344, 345, 374, 390 and 391 of the proposed receptor A and B trisaccharide binding site (VA387 strain) within the P2 domain remained ACR in all partitions, presumably because there was no selective advantage to alter the histo blood group antigens (HBGA) receptor binding specificity. In conclusion, this study provides novel insights to the evolutionary process of norovirus during chronic infection.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
- Kim, MC, et al.
(författare)
-
Development of duck hepatitis A virus type 3 vaccine and its use to protect ducklings against infections
- 2009
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 27:8, s. 6688-6694
-
Tidskriftsartikel (refereegranskat)abstract
- A variant type of duck hepatitis A virus (DHAV), DHAV-3 was recently discovered in South Korea and China. Sequence analyses verified that the variant is genetically or serologically different from the DHAV-1 and DHAV-2 types. Duck hepatitis had been reported in South Korea since 1985 and an attenuated DHAV-1 vaccine had efficiently prevented epidemics of DHAV-1 until 2002. Despite the DHAV-1 based vaccine in use the novel DHAV-3 circulating in South Korea remains to be a threat to duckling farming. To develop a live attenuated vaccine against DHAV-3, a representative isolate, AP-04203, was therefore attenuated by repeated passages in SPF chicken embryos 100 times. The 100th passaged virus, AP-04203P100, did not cause clinical sign and mortality in 1-day-old ducklings as well as reversion of virulence capacity. The ducklings vaccinated with AP-04203P100 virus (10(3.0) ELD(50)/0.2 ml) on 1-day-old age via the intramuscular injection were well protected from 2 days after challenge with pathogenic AP04203P1 virus via the intramuscular route. In addition, the vaccine candidate also exhibited complete protection against currently circulating pathogenic DHAV-3 isolates. In conclusion, we demonstrate that the live attenuated virus, AP-04203P100, is a promising vaccine candidate facilitating the prevention of duck hepatitis caused by DHAV-3 around East Asia including South Korea.
|
|
| 50. |
- Knowles, Charles H., et al.
(författare)
-
Gastrointestinal neuromuscular pathology: guidelines for histological techniques and reporting on behalf of the Gastro 2009 International Working Group
- 2009
-
Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 118:2, s. 271-301
-
Tidskriftsartikel (refereegranskat)abstract
- The term gastrointestinal neuromuscular disease describes a clinically heterogeneous group of disorders of children and adults in which symptoms are presumed or proven to arise as a result of neuromuscular, including interstitial cell of Cajal, dysfunction. Such disorders commonly have impaired motor activity, i.e. slowed or obstructed transit with radiological evidence of transient or persistent visceral dilatation. Whilst sensorimotor abnormalities have been demonstrated by a variety of methods in these conditions, standards for histopathological reporting remain relatively neglected. Significant differences in methodologies and expertise continue to confound the reliable delineation of normality and specificity of particular pathological changes for disease. Such issues require urgent clarification to standardize acquisition and handling of tissue specimens, interpretation of findings and make informed decisions on risk-benefit of full-thickness tissue biopsy of bowel or other diagnostic procedures. Such information will also allow increased certainty of diagnosis, facilitating factual discussion between patients and caregivers, as well as giving prognostic and therapeutic information. The following report, produced by an international working group, using established consensus methodology, presents proposed guidelines on histological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology. The report addresses the main areas of histopathological practice as confronted by the pathologist, including suction rectal biopsy and full-thickness tissue obtained with diagnostic or therapeutic intent. For each, indications, safe acquisition of tissue, histological techniques, reporting and referral recommendations are presented.
|
|
