Journal article
Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
- Abstract:
- Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. Here we use human genome-wide genotyping arrays and new whole-genome HCV viral sequencing technologies to perform a systematic genome-to-genome study of 542 individuals who were chronically infected with HCV, predominantly genotype 3. We show that both alleles of genes encoding human leukocyte antigen molecules and genes encoding components of the interferon lambda innate immune system drive viral polymorphism. Additionally, we show that IFNL4 genotypes determine HCV viral load through a mechanism dependent on a specific amino acid residue in the HCV NS5A protein. These findings highlight the interplay between the innate immune system and the viral genome in HCV control.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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Access Document
- Files:
-
-
(Preview, Accepted manuscript, pdf, 5.7MB, Terms of use)
-
- Publisher copy:
- 10.1038/ng.3835
Authors
+ US National Institutes of Health
More from this funder
- Funding agency for:
- Klenerman, P
- Grant:
- U19AI082630
+ National Institute for Health Research
More from this funder
- Funding agency for:
- Klenerman, P
- Barnes, E
- Grant:
- U19AI082630
+ Medical Research Council
More from this funder
- Funding agency for:
- McLauchlan, J
- Barnes, E
- Grant:
- C0365
- MR/K01532X/1
+ Wellcome Trust
More from this funder
- Funding agency for:
- McVean, G
- Bowden, R
- Klenerman, P
- Spencer, C
- Grant:
- 100956/Z/13/Z
- 090532/Z/09/Z
- U19AI082630
- 097364/Z/11/Z
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Genetics More from this journal
- Volume:
- 49
- Issue:
- 5
- Pages:
- 653-814
- Publication date:
- 2017-04-10
- Acceptance date:
- 2017-03-10
- DOI:
- EISSN:
-
1546-1718
- ISSN:
-
1061-4036
- Language:
-
English
- Keywords:
- Pubs id:
-
pubs:689216
- UUID:
-
uuid:f82608ed-7142-4e4c-9d07-789b16d72c09
- Local pid:
-
pubs:689216
- Source identifiers:
-
689216
- Deposit date:
-
2017-04-26
Terms of use
- Copyright holder:
- Ansari, et al, 2017
- Copyright date:
- 2017
- Notes:
- This is the author accepted manuscript following peer review version of the article. The final version is available online from Nature Publishing Group at: 10.1038/ng.3835
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