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Reversion of CTL escape-variant immunodeficiency viruses in vivo.

Abstract：

:Engendering cytotoxic T-lymphocyte (CTL) responses is likely to be an important goal of HIV vaccines. However, CTLs select for viral variants that escape immune detection. Maintenance of such escape variants in human populations could pose an obstacle to HIV vaccine development. We first observed that escape mutations in a heterogeneous simian immunodeficiency virus (SIV) isolate were lost upon passage to new animals. We therefore infected macaques with a cloned SIV bearing escape mutations in three immunodominant CTL epitopes, and followed viral evolution after infection. Here we show that each mutant epitope sequence continued to evolve in vivo, often re-establishing the original, CTL-susceptible sequence. We conclude that escape from CTL responses may exact a cost to viral fitness. In the absence of selective pressure upon transmission to new hosts, these original escape mutations can be lost. This suggests that some HIV CTL epitopes will be maintained in human populations.

journal_name

Nat Med

journal_title

Nature medicine

authors

Friedrich TC,Dodds EJ,Yant LJ,Vojnov L,Rudersdorf R,Cullen C,Evans DT,Desrosiers RC,Mothé BR,Sidney J,Sette A,Kunstman K,Wolinsky S,Piatak M,Lifson J,Hughes AL,Wilson N,O'Connor DH,Watkins DI

doi

10.1038/nm998

keywords:

subject

Has Abstract

pub_date

2004-03-01 00:00:00

pages

275-81

issue

3

eissn

1078-8956

issn

1546-170X

pii

nm998

journal_volume

10

pub_type

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