Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes
Genetic polymorphism in the interferon lambda (IFN-λ) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to interferon-based treatment. Here, we evaluate associations between IFN-λ polymorphism and HCV variation in 8729 patients (Europeans 77%, Asians 1...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-09-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/42542 |
| _version_ | 1811181102360952832 |
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| author | Nimisha Chaturvedi Evguenia S Svarovskaia Hongmei Mo Anu O Osinusi Diana M Brainard G Mani Subramanian John G McHutchison Stefan Zeuzem Jacques Fellay |
| author_facet | Nimisha Chaturvedi Evguenia S Svarovskaia Hongmei Mo Anu O Osinusi Diana M Brainard G Mani Subramanian John G McHutchison Stefan Zeuzem Jacques Fellay |
| author_sort | Nimisha Chaturvedi |
| collection | DOAJ |
| description | Genetic polymorphism in the interferon lambda (IFN-λ) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to interferon-based treatment. Here, we evaluate associations between IFN-λ polymorphism and HCV variation in 8729 patients (Europeans 77%, Asians 13%, Africans 8%) infected with various viral genotypes, predominantly 1a (41%), 1b (22%) and 3a (21%). We searched for associations between rs12979860 genotype and variants in the NS3, NS4A, NS5A and NS5B HCV proteins. We report multiple associations in all tested proteins, including in the interferon-sensitivity determining region of NS5A. We also assessed the combined impact of human and HCV variation on pretreatment viral load and report amino acids associated with both IFN-λ polymorphism and HCV load across multiple viral genotypes. By demonstrating that IFN-λ variation leaves a large footprint on the viral proteome, we provide evidence of pervasive viral adaptation to innate immune pressure during chronic HCV infection. |
| first_indexed | 2024-04-11T09:14:04Z |
| format | Article |
| id | doaj.art-89cbeb30939249ecbe21013f4a0de48c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:14:04Z |
| publishDate | 2019-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-89cbeb30939249ecbe21013f4a0de48c2022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2019-09-01810.7554/eLife.42542Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypesNimisha Chaturvedi0https://orcid.org/0000-0002-3065-0202Evguenia S Svarovskaia1Hongmei Mo2Anu O Osinusi3Diana M Brainard4G Mani Subramanian5John G McHutchison6Stefan Zeuzem7Jacques Fellay8https://orcid.org/0000-0002-8240-939XSchool of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, SwitzerlandGilead Sciences Inc, Foster City, United StatesGilead Sciences Inc, Foster City, United StatesGilead Sciences Inc, Foster City, United StatesGilead Sciences Inc, Foster City, United StatesGilead Sciences Inc, Foster City, United StatesGilead Sciences Inc, Foster City, United StatesGoethe University Hospital, Frankfurt, GermanySchool of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Precision Medicine Unit, Lausanne University Hospital, Lausanne, SwitzerlandGenetic polymorphism in the interferon lambda (IFN-λ) region is associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to interferon-based treatment. Here, we evaluate associations between IFN-λ polymorphism and HCV variation in 8729 patients (Europeans 77%, Asians 13%, Africans 8%) infected with various viral genotypes, predominantly 1a (41%), 1b (22%) and 3a (21%). We searched for associations between rs12979860 genotype and variants in the NS3, NS4A, NS5A and NS5B HCV proteins. We report multiple associations in all tested proteins, including in the interferon-sensitivity determining region of NS5A. We also assessed the combined impact of human and HCV variation on pretreatment viral load and report amino acids associated with both IFN-λ polymorphism and HCV load across multiple viral genotypes. By demonstrating that IFN-λ variation leaves a large footprint on the viral proteome, we provide evidence of pervasive viral adaptation to innate immune pressure during chronic HCV infection.https://elifesciences.org/articles/42542genome to genome analysisHepatitis Cinterferon lambda polymorphismintegration analysis |
| spellingShingle | Nimisha Chaturvedi Evguenia S Svarovskaia Hongmei Mo Anu O Osinusi Diana M Brainard G Mani Subramanian John G McHutchison Stefan Zeuzem Jacques Fellay Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes eLife genome to genome analysis Hepatitis C interferon lambda polymorphism integration analysis |
| title | Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes |
| title_full | Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes |
| title_fullStr | Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes |
| title_full_unstemmed | Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes |
| title_short | Adaptation of hepatitis C virus to interferon lambda polymorphism across multiple viral genotypes |
| title_sort | adaptation of hepatitis c virus to interferon lambda polymorphism across multiple viral genotypes |
| topic | genome to genome analysis Hepatitis C interferon lambda polymorphism integration analysis |
| url | https://elifesciences.org/articles/42542 |
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