|
|
Abstract
A CYTOPLASMIC DOMAIN FUSION PROTEIN OF THE TRANSMEMBRANE GLYCOPROTEIN GP41 CONFERS DOMINANT INTERFERENCE WITH HUMAN IMMUNODEFICIENCY TYPE 1 VIRUS INFECTIVITY
S. Chen, W. Chan
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan, Republic of China
The cytoplasmic domain of the human immunodeficiency type 1 virus (HIV-1) transmembrane envelope (Env) glycoprotein gp41 was determined to interact with the viral matrix (MA) protein during virus assembly/budding. In addition, we have shown that the cytoplasmic domain of gp41 possesses the potential to self-assemble into a high-ordered multimeric structure and to interact with cellular membranes. These cytoplasmic tail-based viral protein-protein interactions may represent potential targets for the design of therapeutic strategies against HIV-1 infection. A recombinant protein containing the cytoplasmic domain fused to the C terminus of E. coli (-galactosidase, but not (-galactosidase itself, exerted dominant interference with infectious virus production in a dose-dependent manner when coexpressed with the Env protein. Coexpression of (-gal/706-856 with the Env and Gag proteins reduced cell-associated Env and Gag levels compared to those observed in the control, which did not express (-gal, and in (-gal coexpression. Virion-associated gp120 and gp41 levels were also reduced, whereas virion-associated Gag levels were not, or were only slightly, decreased by (-gal/706-856 coexpression. In contrast, (-gal/706-856 did not affect Env expression in the absence of Gag expression. These results taken together demonstrate that the dominant interference with infectious virus production by (-gal/706-856 occurs through down-regulation of steady-state Env expression in a gag gene-dependent manner. The study also suggests that the gp41 cytoplasmic tail may serve as a suitable target for the design of gene-based anti-HIV-1 therapeutic approaches.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
339
Suggested Citation
" S. Chen, et al.
A CYTOPLASMIC DOMAIN FUSION PROTEIN OF THE TRANSMEMBRANE GLYCOPROTEIN GP41 CONFERS DOMINANT INTERFERENCE WITH HUMAN IMMUNODEFICIENCY TYPE 1 VIRUS INFECTIVITY.
Poster:
The 2nd IAS Conference on HIV Pathogenesis and Treatment:
Abstract no.
339"
|
|
|