Elucidation of hepatitis C virus transmission and early diversification by single genome sequencing.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

A precise molecular identification of transmitted hepatitis C virus (HCV) genomes could illuminate key aspects of transmission biology, immunopathogenesis and natural history. We used single genome sequencing of 2,922 half or quarter genomes from plasma viral RNA to identify transmitted/founder (T/F) viruses in 17 subjects with acute community-acquired HCV infection. Sequences from 13 of 17 acute subjects, but none of 14 chronic controls, exhibited one or more discrete low diversity viral lineages. Sequences within each lineage generally revealed a star-like phylogeny of mutations that coalesced to unambiguous T/F viral genomes. Numbers of transmitted viruses leading to productive clinical infection were estimated to range from 1 to 37 or more (median = 4). Four acutely infected subjects showed a distinctly different pattern of virus diversity that deviated from a star-like phylogeny. In these cases, empirical analysis and mathematical modeling suggested high multiplicity virus transmission from individuals who themselves were acutely infected or had experienced a virus population bottleneck due to antiviral drug therapy. These results provide new quantitative and qualitative insights into HCV transmission, revealing for the first time virus-host interactions that successful vaccines or treatment interventions will need to overcome. Our findings further suggest a novel experimental strategy for identifying full-length T/F genomes for proteome-wide analyses of HCV biology and adaptation to antiviral drug or immune pressures.

Full Text

Duke Authors

Cited Authors

  • Li, H; Stoddard, MB; Wang, S; Blair, LM; Giorgi, EE; Parrish, EH; Learn, GH; Hraber, P; Goepfert, PA; Saag, MS; Denny, TN; Haynes, BF; Hahn, BH; Ribeiro, RM; Perelson, AS; Korber, BT; Bhattacharya, T; Shaw, GM

Published Date

  • 2012

Published In

Volume / Issue

  • 8 / 8

Start / End Page

  • e1002880 -

PubMed ID

  • 22927816

Pubmed Central ID

  • PMC3426529

Electronic International Standard Serial Number (EISSN)

  • 1553-7374

Digital Object Identifier (DOI)

  • 10.1371/journal.ppat.1002880


  • eng

Conference Location

  • United States