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

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2009 May 29

PMID 19474106

Citations 85

Authors

Liwei Rong

Jianyong Zhang

Jennifer Lu

Qinghua Pan

Rene-Pierre Lorgeoux

Claudette Aloysius

Fei Guo

Shan-Lu Liu

Mark A Wainberg

Chen Liang

Affiliations

Soon will be listed here.

Abstract

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.

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