The Transmembrane Domain of BST-2 Determines Its Sensitivity to Down-Modulation by Human Immunodeficiency Virus Type 1 Vpu

被引：102

作者：

Rong, Liwei ^{[1
]}

Zhang, Jianyong ^{[1
,2
]}

Lu, Jennifer ^{[1
,2
]}

Pan, Qinghua ^{[1
]}

Lorgeoux, Rene-Pierre ^{[1
,3
]}

Aloysius, Claudette ^{[3
]}

Guo, Fei ^{[4
]}

Liu, Shan-Lu ^{[3
]}

Wainberg, Mark A. ^{[1
,2
,3
]}

Liang, Chen ^{[1
,2
,3
]}

机构：

[1] Jewish Gen Hosp, Lady Davis Inst, McGill AIDS Ctr, Montreal, PQ H3T 1E2, Canada

[2] McGill Univ, Dept Med, Montreal, PQ H3A 2B4, Canada

[3] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada

[4] Chinese Acad Med Sci, Inst Pathogen Biol, State Key Lab Mol Virol & Genet Engn, Beijing 100730, Peoples R China

来源：

JOURNAL OF VIROLOGY | 2009年 / 83卷 / 15期

基金：

加拿大健康研究院;

关键词：

INHIBITS HIV-1; RESTRICTION FACTOR; MEMBRANE-PROTEIN; CELL-SURFACE; RELEASE; DEGRADATION; INFECTION; APOBEC3G; MOTIF;

D O I：

10.1128/JVI.00620-09

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Bone marrow stromal cell antigen 2 (BST-2, also known as tetherin) restricts the production of a number of enveloped viruses by blocking virus release from the cell surface. This antiviral activity is counteracted by such viral factors as Vpu of human immunodeficiency virus type 1 (HIV-1). Here, we report that Vpu antagonizes human BST-2 but not BST-2 derived from African green monkeys. The determinants of susceptibility to Vpu map to the transmembrane domain of BST-2. In accordance with this, expression of human BST-2 containing a modified transmembrane domain effectively blocks the replication of wild-type Vpu-expressing HIV-1 in CD4(+) T cells. Furthermore, these BST-2 variants, as opposed to wild-type human BST-2, are refractory to Vpu-mediated down-regulation as a result of an attenuated interaction with Vpu. In view of the work by others pointing to a key role of the transmembrane domain of Vpu in promoting virus release, our data suggest that a direct interaction through the transmembrane domain of each of these two proteins is a prerequisite for Vpu to down-modulate BST-2.

引用

页码：7536 / 7546

页数：11

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