Vaccination reduces simian-human immunodeficiency virus sequence reversion through enhanced viral control.

Abstract:

:It has been suggested that vaccination prior to infection may direct the mutational evolution of human immunodeficiency virus type 1 (HIV-1) to a less fit virus, resulting in an attenuated course of disease. The present study was initiated to explore whether prior immunization might prevent the reversion of the virus to the wild-type form. Mamu-A*01 monkeys were vaccinated to generate a cytotoxic T-lymphocyte response to the immunodominant Gag p11C epitope and were then challenged with a cloned pathogenic CXCR4-tropic simian-human immunodeficiency virus (SHIV) expressing a mutant Gag p11C sequence (Δp11C SHIV). The epitopic and extraepitopic compensatory mutations introduced into gag of Δp11C SHIV resulted in attenuated replicative capacity and eventual reversions to the wild-type Gag p11C sequence in naïve rhesus monkeys. However, in vaccinated rhesus monkeys, no reversions of the challenge virus were observed, an effect that may have been a consequence of significantly decreased viral replication rather than a redirection of the mutational evolution of the virus. These findings highlight the multifactorial pressures that affect the evolution of primate immunodeficiency viruses.

journal_name

J Virol

journal_title

Journal of virology

authors

Manuel ER,Yeh WW,Balachandran H,Clarke RH,Lifton MA,Letvin NL

doi

10.1128/JVI.01193-10

subject

Has Abstract

pub_date

2010-12-01 00:00:00

pages

12782-9

issue

24

eissn

0022-538X

issn

1098-5514

pii

JVI.01193-10

journal_volume

84

pub_type

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