Interferon lambda 4 impacts the genetic diversity of hepatitis C virus
| Autor: | Ansari, M, Aranday-Cortes, E, Ip, C, Da Silva Filipe, A, Lau, S, Bamford, C, Bonsall, D, Trebes, A, Piazza, P, Sreenu, V, Cowton, V, Consortium, Stop-Hcv, Ball, J, Barnes, E, Burgess, G, Cooke, G, Dillon, J, Foster, G, Gore, C, Guha, N, Halford, R, Holmes, C, Hudson, E, Hutchinson, S, Irving, W, Khakoo, S, Klenerman, P, Martin, N, Mbisa, T, McKeating, J, McLauchlan, J, Miners, A, Murray, A, Shaw, P, Simmonds, P, Smith, S, Spencer, C, Thomson, E, Troke, P, Vickerman, P, Zitzmann, N, Bowden, R, Patel, A, Agarwal, K, Pedergnana, V |
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| Přispěvatelé: | University of Oxford, University of Glasgow, University of Glascow, Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), Queen Mary University of London (QMUL), University of Nottingham, UK (UON), King's College Hospital (KCH), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), National Institute for Health Research |
| Rok vydání: | 2019 |
| Předmět: |
Life Sciences & Biomedicine - Other Topics
hepatitis C virus 0301 basic medicine CLEARANCE MESH: Selection Genetic viruses IL28B Genome-wide association study 0601 Biochemistry and Cell Biology medicine.disease_cause interferon lambda 4 MESH: Genotype 0302 clinical medicine E2 Interferon INFECTION host-pathogen interactions genetics MESH: Hepacivirus MESH: Genetic Variation Biology (General) innate immunity SCAVENGER RECEPTOR-BI MESH: Immunologic Factors General Neuroscience SINGLE-NUCLEOTIDE POLYMORPHISMS General Medicine Acquired immune system 3. Good health Medicine MESH: Viral Load Life Sciences & Biomedicine Viral load medicine.drug MESH: Antiviral Agents MESH: Interleukins QH301-705.5 Science infectious disease Hepatitis C virus MESH: Whites virus Human leukocyte antigen Biology General Biochemistry Genetics and Molecular Biology Virus 03 medical and health sciences genomics medicine human Genetic variability GENOME-WIDE ASSOCIATION genome-to-genome analysis MESH: Hepatitis C Science & Technology MESH: Humans General Immunology and Microbiology FALSE DISCOVERY microbiology MESH: Host-Pathogen Interactions Virology ALPHA 030104 developmental biology MESH: Genome-Wide Association Study INTERLEUKIN 28B STOP-HCV Consortium [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology 030217 neurology & neurosurgery |
| Zdroj: | eLife eLife, 2019, 8, pp.e42463. ⟨10.7554/eLife.42463⟩ eLife, Vol 8 (2019) |
| ISSN: | 2050-084X |
| Popis: | International audience; Hepatitis C virus (HCV) is a highly variable pathogen that frequently establishes chronic infection. This genetic variability is affected by the adaptive immune response but the contribution of other host factors is unclear. Here, we examined the role played by interferon lambda-4 (IFN-λ4) on HCV diversity; IFN-λ4 plays a crucial role in spontaneous clearance or establishment of chronicity following acute infection. We performed viral genome-wide association studies using human and viral data from 485 patients of white ancestry infected with HCV genotype 3a. We demonstrate that combinations of host genetic variants, which determine IFN-λ4 protein production and activity, influence amino acid variation across the viral polyprotein - not restricted to specific viral proteins or HLA restricted epitopes - and modulate viral load. We also observed an association with viral di-nucleotide proportions. These results support a direct role for IFN-λ4 in exerting selective pressure across the viral genome, possibly by a novel mechanism. |
| Databáze: | OpenAIRE |
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