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Journal of Virology, August 2009, p. 7536-7546, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00620-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Liwei Rong,1 Jianyong Zhang,1,2 Jennifer Lu,1,2 Qinghua Pan,1 René-Pierre Lorgeoux,1,3 Claudette Aloysius,3 Fei Guo,4 Shan-Lu Liu,3 Mark A. Wainberg,1,2,3 and Chen Liang1,2,3*

McGill AIDS Centre, Lady Davis Institute—Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2,1 Departments of Medicine,2 Microbiology and Immunology, McGill University, Montreal, Quebec, Canada H3A 2B4,3 State Key Laboratory for Molecular Virology and Genetic Engineering, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China 1007304

Received 25 March 2009/ Accepted 18 May 2009

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.

* Corresponding author. Mailing address: McGill AIDS Centre, Lady Davis Institute—Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7537. E-mail: chen.liang{at}mcgill.ca

{triangledown} Published ahead of print on 27 May 2009.

Journal of Virology, August 2009, p. 7536-7546, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00620-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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