Genomic characterization of hepatitis C virus transmitted founder variants with deep sequencing.
Hepatitis C virus
InC3 study
Next generation sequencing
People who inject drugs
Transmitted-founder virus
Journal
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
ISSN: 1567-7257
Titre abrégé: Infect Genet Evol
Pays: Netherlands
ID NLM: 101084138
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
02
12
2018
revised:
26
02
2019
accepted:
28
02
2019
pubmed:
12
3
2019
medline:
11
2
2020
entrez:
12
3
2019
Statut:
ppublish
Résumé
Transfer of hepatitis C virus (HCV) infection from a donor to a new recipient is associated with a bottleneck of genetic diversity in the transmitted viral variants. Existing data suggests that one, or very few, variants emerge from this bottleneck to establish the infection (transmitted founder [T/F] variants). In HCV, very few T/F variants have been characterized due to the challenges of obtaining early infection samples and of high throughput viral genome sequencing. This study used a large, acute HCV, deep-sequenced dataset from first viremia samples collected in nine prospective cohorts across four countries, to estimate the prevalence of single T/F viruses, and to identify host and virus-related factors associated with infections initiated by a single T/F variant. The short reads generated by Illumina sequencing were used to reconstruct viral haplotypes with two haplotype reconstruction algorithms. The haplotypes were examined for random mutations (Poisson distribution) and a star-like phylogeny to identify T/F viruses. The findings were cross-validated by haplotype reconstructions across three regions of the genome (Core-E2, NS3, NS5A) to minimize the possibility of spurious overestimation of single T/F variants. Of 190 acute infection samples examined, 54 were very early acute infections (HCV antibody negative, RNA positive), and single transmitted founders were identified in 14 (26%, 95% CI: 16-39%) after cross validation across multiple regions of the genome with two haplotype reconstruction algorithms. The presence of a single T/F virus was not associated with any host or virus-related factors, notably viral genotype or spontaneous clearance. In conclusion, approximately one in four new HCV infections originates from a single T/F virus. Resolution of genomic sequences of single T/F variants is the first step in exploring unique properties of these variants in the infection of host hepatocytes.
Identifiants
pubmed: 30853512
pii: S1567-1348(18)30936-5
doi: 10.1016/j.meegid.2019.02.032
pmc: PMC6487228
mid: NIHMS1524442
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
36-41Subventions
Organisme : NIDA NIH HHS
ID : R01 DA015999
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA031056
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA016017
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI066345
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI105035
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI131314
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI088791
Pays : United States
Organisme : CIHR
ID : MOP-103138
Pays : Canada
Organisme : CIHR
ID : MOP-106468
Pays : Canada
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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