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

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Title: Genome-to-genome analysis highlights the effect of the human innate and adaptive immune systems on the hepatitis C virus
Authors: Ansari, A
Pedergnana, V
Ip, C
Magri, A
Von Delft, A
Bonsall, D
Chaturvedi, N
Bartha, I
Smith, D
Nicholson, D
McVean, G
Trebes, A
Piazza, P
Fellay, J
Cooke, GS
Foster, G
STOPHCV consortium
Hudson, E
McLauchlan, J
Simmonds, P
Bowden, R
Klenerman, P
Barnes, E
Spencer, C
Item Type: Journal Article
Abstract: Outcomes of hepatitis C virus (HCV) infection and treatment depend on viral and host genetic factors. 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 chronically infected with HCV, predominately genotype 3. We show that both HLA alleles and interferon lambda innate immune system genes drive viral genome polymorphism, and that IFNL4 genotypes determine HCV viral load through a mechanism that is dependent on a specific polymorphism in the HCV polyprotein. We highlight the interplay between innate immune responses and the viral genome in HCV control.
Issue Date: 10-Apr-2017
Date of Acceptance: 20-Feb-2017
URI: http://hdl.handle.net/10044/1/44869
DOI: https://dx.doi.org/10.1038/ng.3835
ISSN: 1546-1718
Publisher: Nature Publishing Group
Start Page: 666
End Page: 673
Journal / Book Title: Nature Genetics
Volume: 49
Copyright Statement: Copyright © 2017, Rights Managed by Nature Publishing Group
Sponsor/Funder: National Institute for Health Research
Medical Research Council (MRC)
National Institute for Health Research
Medecins Sans Frontieres (MSF)
Funder's Grant Number: RDB21
MR/K01532X/1
EME 14/02/17
PO 08216589
Keywords: Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
DIRECT-ACTING ANTIVIRALS
WIDE ASSOCIATION
GENOTYPES 1
GENETIC-VARIATION
HCV CLEARANCE
DISEASE ASSOCIATION
INTERFERON
INFECTION
IL28B
RESISTANCE
Adaptive Immunity
Alleles
Genetic Variation
Genome, Human
Genome, Viral
Genotype
HLA Antigens
Hepacivirus
Hepatitis C, Chronic
Host-Pathogen Interactions
Humans
Immunity, Innate
Interleukins
Logistic Models
Principal Component Analysis
Viral Load
Viral Nonstructural Proteins
STOP-HCV Consortium
11 Medical And Health Sciences
06 Biological Sciences
Developmental Biology
Publication Status: Published
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



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