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PMID: 19474106 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The transmembrane domain of BST-2 determines its sensitivity to down-modulation by human immunodeficiency virus type 1 Vpu.

Journal of virology ·Vol. 83 ·No. 15 ·2009-08-00 ·Pages 7536-46

Rong L, Zhang J, Lu J, Pan Q, Lorgeoux RP, Aloysius C, Guo F, Liu SL, Wainberg MA, Liang C

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.

MeSH Terms
Amino Acid Sequence Animals Antigens, CD/chemistry,genetics,metabolism COS Cells Chlorocebus aethiops Down-Regulation GPI-Linked Proteins Gene Expression HIV Infections/genetics,metabolism,virology HIV-1/genetics,metabolism HeLa Cells Human Immunodeficiency Virus Proteins/genetics,metabolism Humans Macaca mulatta Membrane Glycoproteins/chemistry,genetics,metabolism Molecular Sequence Data Protein Binding Protein Structure, Tertiary Sequence Alignment Viral Regulatory and Accessory Proteins/genetics,metabolism
Chemicals
Antigens, CD BST2 protein, human GPI-Linked Proteins Human Immunodeficiency Virus Proteins Membrane Glycoproteins Viral Regulatory and Accessory Proteins vpu protein, Human immunodeficiency virus 1
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Rong Liwei
McGill AIDS Centre, Lady Davis Institute-Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2.
Zhang Jianyong
Lu Jennifer
Pan Qinghua
Lorgeoux René-Pierre
Aloysius Claudette
Guo Fei
Liu Shan-Lu
Wainberg Mark A
Liang Chen
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
1098-5514
DOI
10.1128/JVI.00620-09
Published
2009-08-00
Epub
2009-00-27
Pages
7536-46
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC2708638
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.00620-09 PMC Full Text View journal details
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