Viral fitness implications of variation within an immunodominant CD8+ T-cell epitope of HIV-1.

Abstract:

:Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness. Constructs recapitulating in vivo SL9-CTL escape variants showed markedly little effect on replication and fitness, as did non-natural conservative mutations targeting immunologically relevant positions of the epitope. Although certain residues of the epitope were constrained by viral requirements, our research reveals that there are multiple SL9 variants that are well tolerated virologically but fail to arise in vivo. In light of this data, assumptions regarding the balance of immune and viral selective pressures on this immunodominant epitope sequence need to be reassessed.

journal_name

Virology

journal_title

Virology

authors

Christie NM,Willer DO,Lobritz MA,Chan JK,Arts EJ,Ostrowski MA,Cochrane A,Luscher MA,MacDonald KS

doi

10.1016/j.virol.2009.03.003

subject

Has Abstract

pub_date

2009-05-25 00:00:00

pages

137-46

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(09)00178-0

journal_volume

388

pub_type

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