HLA-B Signal Peptide Polymorphism Influences the Rate of HIV-1 Acquisition but Not Viral Load

被引：30
|
作者：
Merino, Aimee M. [1 ,2 ]
Song, Wei [1 ]
He, Dongning [1 ]
Mulenga, Joseph [4 ]
Allen, Susan [4 ,5 ]
Hunter, Eric [6 ]
Tang, Jianming [1 ,2 ]
Kaslow, Richard A. [1 ,2 ,3 ]
机构：
[1] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[2] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
[3] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA
[4] Rwanda Zambia HIV 1 Res Grp, Lusaka, Zambia
[5] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[6] Emory Univ, Vaccine Res Ctr, Atlanta, GA 30322 USA
来源：
JOURNAL OF INFECTIOUS DISEASES | 2012年 / 205卷 / 12期
关键词：
IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE ANTIGEN (HLA)-E; NATURAL-KILLER-CELLS; SEQUENCE-DERIVED PEPTIDES; CLASS-I; SURFACE EXPRESSION; DISCORDANT COUPLES; ZAMBIAN COUPLES; MEDIATED LYSIS; E BINDS;
D O I：
10.1093/infdis/jis275
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Human leukocyte antigen alleles influence the immune response to HIV-1. Signal peptides cleaved from those alleles bind to HLA-E and mediate natural killer cell function. Signal peptides of HLA-A and HLA-C proteins carry methionine (Met) at anchor position 2 (P2); those of HLA-B carry Met or threonine (Thr). Different P2 residues alter HLA-E binding to its cognate receptors and may impact HIV-1 acquisition. Among Zambian couples (N = 566) serodiscordant for HIV-1, P2-Met accelerated acquisition in the HIV-1-negative partner (relative hazard [RH], 1.79). Among seroconverting Zambian (n = 240) and Rwandan (n = 64) partners, P2-Met also accelerated acquisition (RH, 1.47 and RH, 1.83 respectively). HLA-B alleles displaying the reportedly protective Bw4 epitope carry P2-Thr. Bw4/P2-Thr and Bw6/P2-Thr showed similar protective effects compared with Bw6/P2-Met. Neither motif was associated with viral load. The influence of HLA-B alleles on HIV/AIDS may derive from multiple motifs in and beyond the mature proteins.
引用
收藏
页码：1797 / 1805
页数：9
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