BST-2 mediated restriction of simian-human immunodeficiency virus

Autumn Ruiz; David Lau; Richard S. Mitchell; M. Sarah Hill; Kimberly Schmitt; John C. Guatelli; Edward B. Stephens

doi:10.1016/j.virol.2010.07.021

BST-2 mediated restriction of simian-human immunodeficiency virus

Autumn Ruiz, David Lau, Richard S. Mitchell, M. Sarah Hill, Kimberly Schmitt, John C. Guatelli, Edward B. Stephens

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Pathogenic simian-human immunodeficiency viruses (SHIV) contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential "humanization" of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.

Original language	English (US)
Pages (from-to)	312-321
Number of pages	10
Journal	Virology
Volume	406
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2010.07.021
State	Published - Oct 2010

Keywords

BST-2
HIV-1
Pig-tailed macaque
Rhesus macaque
SHIV
Simian-human immunodeficiency virus
Transmembrane domain
Virus release
Vpu

ASJC Scopus subject areas

Virology

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title = "BST-2 mediated restriction of simian-human immunodeficiency virus",

abstract = "Pathogenic simian-human immunodeficiency viruses (SHIV) contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential {"}humanization{"} of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.",

keywords = "BST-2, HIV-1, Pig-tailed macaque, Rhesus macaque, SHIV, Simian-human immunodeficiency virus, Transmembrane domain, Virus release, Vpu",

author = "Autumn Ruiz and David Lau and Mitchell, {Richard S.} and Hill, {M. Sarah} and Kimberly Schmitt and Guatelli, {John C.} and Stephens, {Edward B.}",

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AU - Ruiz, Autumn

AU - Lau, David

AU - Mitchell, Richard S.

AU - Hill, M. Sarah

AU - Schmitt, Kimberly

AU - Guatelli, John C.

AU - Stephens, Edward B.

PY - 2010/10

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N2 - Pathogenic simian-human immunodeficiency viruses (SHIV) contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential "humanization" of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.

AB - Pathogenic simian-human immunodeficiency viruses (SHIV) contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential "humanization" of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.

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KW - Rhesus macaque

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KW - Transmembrane domain

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