High-Resolution Evolutionary Analysis of Within-Host Hepatitis C Virus Infection.
Antiviral Agents
/ pharmacology
Coinfection
Drug Resistance, Viral
Evolution, Molecular
Genetic Variation
Genetics, Population
Genotype
HIV Infections
/ virology
HIV-1
/ genetics
Hepacivirus
/ genetics
Hepatitis C
/ virology
Hepatitis C, Chronic
/ virology
High-Throughput Nucleotide Sequencing
Humans
Molecular Epidemiology
Recombination, Genetic
Virus Replication
hepatitis C virus
molecular epidemiology
phylogenetics
population genetics
recombination
viral evolution
viral replication
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
05 05 2019
05 05 2019
Historique:
received:
18
09
2018
accepted:
28
12
2018
pubmed:
3
1
2019
medline:
17
3
2020
entrez:
3
1
2019
Statut:
ppublish
Résumé
Despite recent breakthroughs in treatment of hepatitis C virus (HCV) infection, we have limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap is important for identifying the main sources of disease transmission and evaluating the risk of drug-resistance mutations emerging and disseminating in a population. We have undertaken a high-resolution analysis of HCV within-host evolution from 4 individuals coinfected with human immunodeficiency virus 1 (HIV-1). We used long-read, deep-sequenced data of full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral population and evolutionary dynamics. We found statistical support for population structure maintaining the within-host HCV genetic diversity in 3 out of 4 individuals. We also report the first population genetic estimate of the within-host recombination rate for HCV (0.28 × 10-7 recombination/site/year), which is considerably lower than that estimated for HIV-1 and the overall nucleotide substitution rate estimated during HCV infection. Our findings indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale.
Sections du résumé
BACKGROUND
Despite recent breakthroughs in treatment of hepatitis C virus (HCV) infection, we have limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap is important for identifying the main sources of disease transmission and evaluating the risk of drug-resistance mutations emerging and disseminating in a population.
METHODS
We have undertaken a high-resolution analysis of HCV within-host evolution from 4 individuals coinfected with human immunodeficiency virus 1 (HIV-1). We used long-read, deep-sequenced data of full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral population and evolutionary dynamics.
RESULTS
We found statistical support for population structure maintaining the within-host HCV genetic diversity in 3 out of 4 individuals. We also report the first population genetic estimate of the within-host recombination rate for HCV (0.28 × 10-7 recombination/site/year), which is considerably lower than that estimated for HIV-1 and the overall nucleotide substitution rate estimated during HCV infection.
CONCLUSIONS
Our findings indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale.
Identifiants
pubmed: 30602023
pii: 5269822
doi: 10.1093/infdis/jiy747
pmc: PMC6500553
mid: EMS81302
doi:
Substances chimiques
Antiviral Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1722-1729Subventions
Organisme : Wellcome Trust
ID : 107652
Pays : United Kingdom
Organisme : European Research Council
ID : 614725
Pays : International
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
Références
J Hepatol. 2014 Nov;61(1 Suppl):S45-57
pubmed: 25086286
J Gen Virol. 2005 Oct;86(Pt 10):2781-2786
pubmed: 16186232
J Virol. 2017 Feb 28;91(6):
pubmed: 28077634
Genetics. 2002 Sep;162(1):395-411
pubmed: 12242249
Gastroenterology. 2014 May;146(5):1176-92
pubmed: 24631495
PLoS Comput Biol. 2014 Apr 10;10(4):e1003537
pubmed: 24722319
Virus Evol. 2016 Mar 02;2(1):vew003
pubmed: 27774296
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14562-7
pubmed: 22829669
PLoS Pathog. 2016 Sep 15;12(9):e1005894
pubmed: 27631086
PLoS Comput Biol. 2010 Jan 29;6(1):e1000660
pubmed: 20126527
BMC Evol Biol. 2011 May 19;11:131
pubmed: 21595904
Mol Biol Evol. 2005 May;22(5):1185-92
pubmed: 15703244
J Virol. 2012 Aug;86(16):8432-9
pubmed: 22623804
Nat Rev Genet. 2009 Aug;10(8):540-50
pubmed: 19564871
Genetics. 1994 Jun;137(2):597-606
pubmed: 8070669
Evolution. 1981 May;35(3):477-488
pubmed: 28563585
Infect Genet Evol. 2018 Mar;58:77-82
pubmed: 29253674
Proc Natl Acad Sci U S A. 2006 May 30;103(22):8475-80
pubmed: 16707577
PLoS Genet. 2015 Aug 12;11(8):e1005421
pubmed: 26267488
Mol Biol Evol. 2006 Jan;23(1):7-9
pubmed: 16177232
PLoS Med. 2015 Nov 03;12(11):e1001898; discussion e1001898
pubmed: 26529093
Hepatology. 2019 May;69(5):1861-1872
pubmed: 29425396
Genetics. 1995 Jun;140(2):821-41
pubmed: 7498757
PLoS Biol. 2006 May;4(5):e88
pubmed: 16683862
J Viral Hepat. 2017 May;24(5):404-411
pubmed: 27882678
J Virol. 2012 Dec;86(23):12582-90
pubmed: 22973048
Syst Biol. 2011 Mar;60(2):150-60
pubmed: 21187451
Mol Biol Evol. 2013 Mar;30(3):713-24
pubmed: 23180580
PLoS Pathog. 2012;8(5):e1002656
pubmed: 22570609
Mol Biol Evol. 2012 Aug;29(8):1969-73
pubmed: 22367748
Hepatology. 2018 Sep;68(3):859-871
pubmed: 29534310
J Virol. 2011 Jul;85(13):6369-80
pubmed: 21525348
Science. 1999 Sep 10;285(5434):1745-7
pubmed: 10481012
Virology. 2013 Dec;447(1-2):187-96
pubmed: 24210114
J Virol. 2004 Apr;78(7):3447-54
pubmed: 15016867
J Gen Virol. 2005 Jul;86(Pt 7):1931-1942
pubmed: 15958671
Science. 2000 Apr 14;288(5464):339-44
pubmed: 10764648