ßTrCP is Required for HIV-1 Vpu Modulation of CD4, GaLV Env, and BST-2/Tetherin.
Viruses
; 10(10)2018 10 19.
Article
em En
| MEDLINE
| ID: mdl-30347660
ABSTRACT
The Human immunodeficiency virus-1 (HIV-1) accessory protein Vpu modulates numerous proteins, including the host proteins CD4 and BST-2/tetherin. Vpu interacts with the Skp, Cullin, F-Box (SCF) ubiquitin ligase through interactions with the F-Box protein ßTrCP (1 and/or 2). This interaction is dependent on phosphorylation of S52,56 in Vpu. Mutation of S52,56, or inhibition of the SCF, abolishes most Vpu activity against CD4 and partly reduces activity against BST-2/tetherin. Recently, Vpu has also been reported to interact with the clathrin adapter proteins AP-1 and AP-2, and these interactions were also found to be required for BST-2/tetherin antagonism in an S52,56 -dependent manner. In assays where HIV-1 is pseudotyped with gibbon ape leukemia virus (GaLV Env), Vpu has also been found to prevent GaLV Env from being incorporated into viral particles, but the mechanism for this antagonism is not fully understood. To clarify the role of the ßTrCPs in Vpu function we used CRISPR/Cas9 to generate a clonal cell line lacking both ßTrCP-1 and -2. Vpu activity against CD4 and GaLV Env was abolished in this cell line, and activity against BST-2/tetherin reduced significantly. Mutation of the S52,56 residues no longer affected Vpu activity against BST-2/tetherin in this cell line. These data suggest that the primary role of the S52,56 residues in antagonism of CD4, GaLV Env, and BST-2/tetherin is to recruit the SCF/ßTrCP ubiquitin ligase.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos CD
/
Antígenos CD4
/
Infecções por HIV
/
Proteínas do Envelope Viral
/
HIV-1
/
Proteínas Contendo Repetições de beta-Transducina
/
Proteínas do Vírus da Imunodeficiência Humana
/
Proteínas Virais Reguladoras e Acessórias
Limite:
Humans
Idioma:
En
Revista:
Viruses
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos