当前位置： SCI文献检索 > JOURNAL OF VIROLOGY期刊下所有文献 > HLA class I-driven evolution of human immunodeficiency virus type 1 subtype c proteome: immune escape and viral load.

HLA class I-driven evolution of human immunodeficiency virus type 1 subtype c proteome: immune escape and viral load.

Abstract：

:Human immunodeficiency virus type 1 (HIV-1) mutations that confer escape from cytotoxic T-lymphocyte (CTL) recognition can sometimes result in lower viral fitness. These mutations can then revert upon transmission to a new host in the absence of CTL-mediated immune selection pressure restricted by the HLA alleles of the prior host. To identify these potentially critical recognition points on the virus, we assessed HLA-driven viral evolution using three phylogenetic correction methods across full HIV-1 subtype C proteomes from a cohort of 261 South Africans and identified amino acids conferring either susceptibility or resistance to CTLs. A total of 558 CTL-susceptible and -resistant HLA-amino acid associations were identified and organized into 310 immunological sets (groups of individual associations related to a single HLA/epitope combination). Mutations away from seven susceptible residues, including four in Gag, were associated with lower plasma viral-RNA loads (q < 0.2 [where q is the expected false-discovery rate]) in individuals with the corresponding HLA alleles. The ratio of susceptible to resistant residues among those without the corresponding HLA alleles varied in the order Vpr > Gag > Rev > Pol > Nef > Vif > Tat > Env > Vpu (Fisher's exact test; P < or = 0.0009 for each comparison), suggesting the same ranking of fitness costs by genes associated with CTL escape. Significantly more HLA-B (chi(2); P = 3.59 x 10(-5)) and HLA-C (chi(2); P = 4.71 x 10(-6)) alleles were associated with amino acid changes than HLA-A, highlighting their importance in driving viral evolution. In conclusion, specific HIV-1 residues (enriched in Vpr, Gag, and Rev) and HLA alleles (particularly B and C) confer susceptibility to the CTL response and are likely to be important in the development of vaccines targeted to decrease the viral load.

journal_name

J Virol

journal_title

Journal of virology

authors

Rousseau CM,Daniels MG,Carlson JM,Kadie C,Crawford H,Prendergast A,Matthews P,Payne R,Rolland M,Raugi DN,Maust BS,Learn GH,Nickle DC,Coovadia H,Ndung'u T,Frahm N,Brander C,Walker BD,Goulder PJ,Bhattacharya T,Hecke

doi

10.1128/JVI.02455-07

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

6434-46

issue

eissn

0022-538X

issn

1098-5514

pii

JVI.02455-07

journal_volume

pub_type

杂志文章

在线工具

HLA class I-driven evolution of human immunodeficiency virus type 1 subtype c proteome: immune escape and viral load.