Compensatory mutation partially restores fitness and delays reversion of escpe mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection

被引:184
作者
Crawford, Hayley
Prado, Julia G.
Leslie, Alasdair
Hue, Stephane
Honeyborne, Isobella
Reddy, Sharon
van der Stok, Mary
Mncube, Zenele
Brander, Christian
Rousseau, Christine
Mullins, James I.
Kaslow, Richard
Goepfert, Paul
Allen, Susan
Hunter, Eric
Mulenga, Joseph
Kiepiela, Photini
Walker, Bruce D.
Goulder, Philip J. R.
机构
[1] Univ Oxford, Dept Pediat, Oxford OX1 3SY, England
[2] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, South Africa
[3] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA
[4] Univ Washington, Dept Microbiol, Sch Med, Seattle, WA 98195 USA
[5] Univ Alabama Birmingham, Birmingham, AL 35294 USA
[6] ZEHRG, Lusaka, Zambia
[7] Zambia Blood Transfus Serv, Lusaka, Zambia
[8] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30329 USA
[9] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA
关键词
D O I
10.1128/JVI.00465-07
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
HLA-B*5703 is associated with effective immune control in human immunodeficiency virus type I (HIV-1) infection. Here we describe an escape mutation within the immunodominant HLA-B*5703-restricted epitope in chronic HIV-1 infection, KAFSPEVIPMF (Gag 162-172), and demonstrate that this mutation reduces viral replicative capacity. Reversion of this mutation following transmission to HLA-B*5703-negative recipients was delayed by the compensatory mutation S165N within the same epitope. These data may help explain the observed association between HLA-B*5703 and long-term control of viremia.
引用
收藏
页码:8346 / 8351
页数:6
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