Immunity in chimpanzees chronically infected with hepatitis C virus: role of minor quasispecies in reinfection.

Abstract:

:We have previously reported that chimpanzees chronically infected with hepatitis C virus (HCV) could be reinfected, even with the original infecting strain. In this study we tested the hypothesis that this might reflect the presence of minor quasispecies to which there was little or no immunity. To evaluate this hypothesis, we sequenced multiple clones taken at intervals after primary infection and rechallenge from four chronically infected chimpanzees. The inoculum used in these studies (HCV-H, genotype 1a) revealed 17 separate variants among 46 clones sequenced. Following challenge, each of the four challenged animals showed marked alterations of their quasispecies distribution. The new variants, which appeared 1 to 6 weeks after challenge, were either identical to or closely resembled variants present in the challenge inoculum. These results, paralleled by an increase in viremia in some of the challenged animals, suggest that quasispecies in the challenge inoculum were responsible for signs of reinfection and that there was little immunity. However, the newly emerged quasispecies completely took over infection in only one animal. In the remaining three chimpanzees the prechallenge quasispecies were able to persist. The natural evolution of infection within chimpanzees resulted in variants able to compete with the inoculum variants. Whether through reexposure or the natural progression of infection, newly emerged quasispecies are likely to play a role in the pathogenesis of chronic HCV infection.

journal_name

J Virol

journal_title

Journal of virology

authors

Wyatt CA,Andrus L,Brotman B,Huang F,Lee DH,Prince AM

doi

10.1128/JVI.72.3.1725-1730.1998

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

1725-30

issue

3

eissn

0022-538X

issn

1098-5514

journal_volume

72

pub_type

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