Constraints on viral evolution during chronic hepatitis C virus infection arising from a common-source exposure

Justin Bailey, Sarah Laskey, Lisa N. Wasilewski, Supriya Munshaw, Liam J. Fanning, Elizabeth Kenny-Walsh, Stuart Campbell Ray

Research output: Contribution to journalArticle

Abstract

Extraordinary viral sequence diversity and rapid viral genetic evolution are hallmarks of hepatitis C virus (HCV) infection. Viral sequence evolution has previously been shown to mediate escape from cytotoxic T-lymphocyte (CTL) and neutralizing antibody responses in acute HCV infection. HCV evolution continues during chronic infection, but the pressures driving these changes are poorly defined. We analyzed plasma virus sequence evolution in 5.2-kb hemigenomes from multiple longitudinal time points isolated from individuals in the Irish anti-D cohort, who were infected with HCV from a common source in 1977 to 1978. We found phylogenetically distinct quasispecies populations at different plasma time points isolated late in chronic infection, suggesting ongoing viral evolution and quasispecies replacement over time. We saw evidence of early pressure driving net evolution away from a computationally reconstructed common ancestor, known as Bole1b, in predicted CTL epitopes and E1E2, with balanced evolution toward and away from the Bole1b amino acid sequence in the remainder of the genome. Late in chronic infection, the rate of evolution toward the Bole1b sequence increased, resulting in net neutral evolution relative to Bole1b across the entire 5.2-kb hemigenome. Surprisingly, even late in chronic infection, net amino acid evolution away from the infecting inoculum sequence still could be observed. These data suggest that, late in chronic infection, ongoing HCV evolution is not random genetic drift but rather the product of strong pressure toward a common ancestor and concurrent net ongoing evolution away from the inoculum virus sequence, likely balancing replicative fitness and ongoing immune escape.

Original languageEnglish (US)
Pages (from-to)12582-12590
Number of pages9
JournalJournal of Virology
Volume86
Issue number23
DOIs
StatePublished - Dec 2012

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chronic hepatitis C
Hepatitis C virus
Chronic Hepatitis C
Virus Diseases
Hepacivirus
Genetic Drift
Infection
infection
Cytotoxic T-Lymphocytes
Pressure
Viruses
T-Lymphocyte Epitopes
Molecular Evolution
Neutralizing Antibodies
cytotoxic T-lymphocytes
Antibody Formation
Amino Acid Sequence
Genome
inoculum
ancestry

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Constraints on viral evolution during chronic hepatitis C virus infection arising from a common-source exposure. / Bailey, Justin; Laskey, Sarah; Wasilewski, Lisa N.; Munshaw, Supriya; Fanning, Liam J.; Kenny-Walsh, Elizabeth; Ray, Stuart Campbell.

In: Journal of Virology, Vol. 86, No. 23, 12.2012, p. 12582-12590.

Research output: Contribution to journalArticle

Bailey, Justin ; Laskey, Sarah ; Wasilewski, Lisa N. ; Munshaw, Supriya ; Fanning, Liam J. ; Kenny-Walsh, Elizabeth ; Ray, Stuart Campbell. / Constraints on viral evolution during chronic hepatitis C virus infection arising from a common-source exposure. In: Journal of Virology. 2012 ; Vol. 86, No. 23. pp. 12582-12590.
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