The antiviral factor APOBEC3G enhances the recognition of HIV-infected primary T cells by natural killer cells

被引：85

作者：

Norman, Jason M. ^{[1
]}

Mashiba, Michael ^{[2
]}

McNamara, Lucy A. ^{[1
,3
]}

Onafuwa-Nuga, Adewunmi ^{[4
]}

Chiari-Fort, Estelle ^{[4
]}

Shen, Wenwen ^{[4
]}

Collins, Kathleen L. ^{[1
,2
,4
]}

机构：

[1] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Grad Program Immunol, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA

来源：

NATURE IMMUNOLOGY | 2011年 / 12卷 / 10期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

URACIL-DNA; CYTIDINE DEAMINASE; CUTTING EDGE; HLA-B; VIRUS; NKG2D; DEGRADATION; EXPRESSION; VPR; IDENTIFICATION;

D O I：

10.1038/ni.2087

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

APOBEC3G (A3G) is an intrinsic antiviral factor that inhibits the replication of human immunodeficiency virus (HIV) by deaminating cytidine residues to uridine. This causes guanosine-to-adenosine hypermutation in the opposite strand and results in inactivation of the virus. HIV counteracts A3G through the activity of viral infectivity factor (Vif), which promotes degradation of A3G. We report that viral protein R (Vpr), which interacts with a uracil glycosylase, also counteracted A3G by diminishing the incorporation of uridine. However, this process resulted in activation of the DNA-damage-response pathway and the expression of natural killer (NK) cell-activating ligands. Our results show that pathogen-induced deamination of cytidine and the DNA-damage response to virus-mediated repair of the incorporation of uridine enhance the recognition of HIV-infected cells by NK cells.

引用

页码：975 / U83

页数：11

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