Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.

Ansari, M.A.; Pedergnana, V.; L C Ip, C.; Magri, A.; Von Delft, A.; Bonsall, D.; Chaturvedi, N.; Bartha, I.; Smith, D.; Nicholson, G.; McVean, G.; Trebes, A.; Piazza, P.; Fellay, J.; Cooke, G.; Foster, G.R.; Hudson, E.; McLauchlan, J.; Simmonds, P.; Bowden, R.; Klenerman, P.; Barnes, E.; Spencer, CCA

doi:10.1038/ng.3835

Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.

Details

Download: 28394351_BIB_179F1128ACCA.pdf (2313.36 [Ko])
State: Public
Version: Author's accepted manuscript
License: Not specified

Serval ID

serval:BIB_179F1128ACCA

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus.

Journal

Nature genetics

Author(s)

Ansari M.A., Pedergnana V., L C Ip C., Magri A., Von Delft A., Bonsall D., Chaturvedi N., Bartha I., Smith D., Nicholson G., McVean G., Trebes A., Piazza P., Fellay J., Cooke G., Foster G.R., Hudson E., McLauchlan J., Simmonds P., Bowden R., Klenerman P., Barnes E., Spencer CCA

Working group(s)

STOP-HCV Consortium

Contributor(s)

Barnes E., Ball J., Brainard D., Burgess G., Cooke G., Dillon J., Foster G.R., Gore C., Guha N., Halford R., Herath C., Holmes C., Howe A., Hudson E., Irving W., Khakoo S., Klenerman P., Koletzki D., Martin N., Massetto B., Mbisa T., McHutchison J., McKeating J., McLauchlan J., Miners A., Murray A., Shaw P., Simmonds P., Spencer CCA, Targett-Adams P., Thomson E., Vickerman P., Zitzmann N.

ISSN

1546-1718 (Electronic)

ISSN-L

1061-4036

Publication state

Published

Issued date

05/2017

Peer-reviewed

Oui

Volume

Number

Pages

666-673

Language

english

Notes

Publication types: Journal Article
Publication Status: ppublish

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.

Keywords

Adaptive Immunity/genetics, Alleles, Genetic Variation, Genome, Human/genetics, Genome, Viral/genetics, Genotype, HLA Antigens/genetics, Hepacivirus/genetics, Hepacivirus/physiology, Hepatitis C, Chronic/genetics, Hepatitis C, Chronic/virology, Host-Pathogen Interactions/genetics, Humans, Immunity, Innate/genetics, Interleukins/genetics, Logistic Models, Principal Component Analysis, Viral Load/genetics, Viral Nonstructural Proteins/genetics

URN

urn:nbn:ch:serval-BIB_179F1128ACCA9

OAI-PMH

oai:serval.unil.ch:BIB_179F1128ACCA

DOI

10.1038/ng.3835

Pubmed

28394351

Web of science

000400051400006

Publisher's website

http://europepmc.org/abstract/med/28394351