Functional antagonism of rhesus macaque and chimpanzee BST-2 by HIV-1 Vpu is mediated by cytoplasmic domain interactions.
J Virol
; 87(24): 13825-36, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24109238
ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) Vpu enhances the release of viral particles from infected cells by interfering with the function of BST-2/tetherin, a cellular protein inhibiting virus release. The Vpu protein encoded by NL4-3, a widely used HIV-1 laboratory strain, antagonizes human BST-2 but not monkey or murine BST-2, leading to the conclusion that BST-2 antagonism by Vpu is species specific. In contrast, we recently identified several primary Vpu isolates, such as Vpu of HIV-1DH12, capable of antagonizing both human and rhesus BST-2. Here we report that while Vpu interacts with human BST-2 primarily through their respective transmembrane domains, antagonism of rhesus BST-2 by Vpu involved an interaction of their cytoplasmic domains. Importantly, a Vpu mutant carrying two mutations in its transmembrane domain (A14L and W22A), rendering it incompetent for interaction with human BST-2, was able to interact with human BST-2 carrying the rhesus BST-2 cytoplasmic domain and partially neutralized the ability of this BST-2 variant to inhibit viral release. Bimolecular fluorescence complementation analysis to detect Vpu-BST-2 interactions suggested that the physical interaction of Vpu with rhesus or chimpanzee BST-2 involves a 5-residue motif in the cytoplasmic domain of BST-2 previously identified as important for the antagonism of monkey and great ape BST-2 by simian immunodeficiency virus (SIV) Nef. Thus, our study identifies a novel mechanism of antagonism of monkey and great ape BST-2 by Vpu that targets the same motif in BST-2 used by SIV Nef and might explain the expanded host range observed for Vpu isolates in our previous study.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Infecciones por VIH
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Pan troglodytes
/
VIH-1
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Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral
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Proteínas del Virus de la Inmunodeficiencia Humana
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Proteínas Reguladoras y Accesorias Virales
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Macaca mulatta
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Virol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos