The evolutionary dynamics and epidemiological history of hepatitis C virus genotype 6, including unique strains from the Li community of Hainan Island, China

Xu, R. et al. (2022) The evolutionary dynamics and epidemiological history of hepatitis C virus genotype 6, including unique strains from the Li community of Hainan Island, China. Virus Evolution, 8(1), veac012. (doi: 10.1093/ve/veac012)

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Abstract

Hepatitis C virus (HCV) is a highly diverse pathogen that frequently establishes a chronic long-term infection, but the origins and drivers of HCV diversity in the human population remain unclear. Previously unidentified strains of HCV genotype 6 (gt6) were recently discovered in chronically infected individuals of the Li ethnic group living in Baisha County, Hainan Island, China. The Li community, who were early settlers on Hainan Island, have a distinct host genetic background and cultural identity compared to other ethnic groups on the island and mainland China. In this report, we generated 33 whole virus genome sequences to conduct a comprehensive molecular epidemiological analysis of these novel gt6 strains in the context of gt6 isolates present in Southeast Asia. With the exception of one gt6a isolate, the Li gt6 sequences formed 3 novel clades from two lineages which constituted 3 newly assigned gt6 subtypes and 30 unassigned strains. Using Bayesian inference methods, we dated the most recent common ancestor for all available gt6 whole virus genome sequences to approximately 2767 BCE (95% HPD intervals, 3670 to 1397 BCE), which is far earlier than previous estimates. The substitution rate was 1.20 x 10-4 substitutions/site/year (s/s/y) and this rate varied across the genome regions, from 1.02 x 10-5 s/s/y in the 5ʹUTR region to 3.07 x 10-4 s/s/y in E2. Thus, our study on an isolated ethnic minority group within a small geographical area of Hainan Island has substantially increased the known diversity of HCV gt6, already acknowledged as the most diverse HCV genotype. The extant HCV gt6 sequences from this study were probably transmitted to the Li through at least three independent events dating perhaps from around 4000 years ago. This analysis describes deeper insight into basic aspects of HCV gt6 molecular evolution including the extensive diversity of gt6 sequences in the isolated Li ethnic group.

Item Type:Articles
Additional Information:This study was supported by two grants from National Natural Science Foundation of China (Nos. 81772208 and 32000666), and Guangdong Basic and Applied Basic Research Foundation 2020A1515010118. EAC, ECML, JH, JS, VS, ADS and JM were supported by the UK Medical Research Council (MC_UU_12014/1 and MC_UU_12014/12).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Aranday-Cortes, Dr Elihu and Singer, Dr Josh and Tong, Dr Lily and Xu, Dr Ru and Da Silva Filipe, Dr Ana and Hughes, Dr Joseph and Bamford, Dr Connor and McLauchlan, Professor John
Creator Roles:
Xu, R.Conceptualization, Data curation, Formal analysis, Investigation, Visualization, Writing – original draft, Writing – review and editing
Aranday-Cortes, E.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Visualization, Writing – review and editing
Hughes, J.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review and editing
McLauchlan, J.Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Visualization, Writing – original draft, Writing – review and editing
Singer, J.Data curation, Formal analysis, Methodology, Resources, Software, Writing – review and editing
Tong, L.Investigation, Methodology, Resources
Da Silva Filipe, A.Investigation, Methodology, Supervision, Writing – review and editing
Bamford, C.Investigation, Methodology, Resources
Authors: Xu, R., Aranday-Cortes, E., McWilliam Leitch, E. C., Hughes, J., Singer, J. B., Sreenu, V., Tong, L., Da Silva Filipe, A., Bamford, C. G.G., Rong, X., Huang, J., Wang, M., Fu, Y., 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:Virus Evolution
Publisher:Oxford University Press
ISSN:2057-1577
ISSN (Online):2057-1577
Published Online:16 February 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Virus Evolution 8(1): veac012
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630004The factors that drive HCV evolution and development of an antibody-focused prophylactic HCV vaccine (Programme 3)John McLauchlanMedical Research Council (MRC)MC_UU_12014/1III - Centre for Virus Research
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research