An interferon lambda 4-associated variant in the hepatitis C virus RNA polymerase affects viral replication in infected cells

Bamford, C. G.G. and McLauchlan, J. (2021) An interferon lambda 4-associated variant in the hepatitis C virus RNA polymerase affects viral replication in infected cells. Journal of General Virology, 102(2), 001495. (doi: 10.1099/jgv.0.001495) (PMID:32897180)

Abstract

Host IFNL4 haplotype status contributes to the development of chronic hepatitis C virus infection in individuals who are acutely infected with the virus. In silico studies revealed that specific amino acid variants at multiple sites on the HCV polyprotein correlate with functional single nucleotide polymorphisms (SNPs) in the IFNL4 locus. Thus, SNPs at the IFNL4 locus may select variants that influence virus replication and thereby outcome of infection. Here, we examine the most significantly IFNL4-associated amino acid variants that lie in the ‘Lambda (L) 2 loop’ of the HCV NS5B RNA polymerase. L2 loop variants were introduced into both sub-genomic replicon and full-length infectious clones of HCV and viral replication examined in the presence and absence of exogenous IFNλ4. Our data demonstrate that while mutation of NS5B L2 loop affects replication, individual IFNL4-associated variants have modest but consistent effects on replication both in the presence and absence of IFNλ4. Given the strong genetic association between these variants and IFNL4, these data suggest a nuanced effect of each individual position on viral replication, the combined effect of which might mediate resistance to the effects of IFNλ4.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Bamford, Dr Connor and McLauchlan, Professor John
• Authors: Bamford, C. G.G., and McLauchlan, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Journal of General Virology
• Publisher: Society for General Microbiology
• ISSN: 0022-1317
• ISSN (Online): 1465-2099
• Published Online: 08 September 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Journal of General Virology 102(2): 001495
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
65634	1	Virus-host interactions in hepatitis C virus infection	John McLauchlan	Medical Research Council (MRC)	MC_UU_12014/1	MVLS III - CENTRE FOR VIRUS RESEARCH