Human immunodeficiency virus type 1 Vif‐derived peptides inhibit the viral protease and arrest virus production

FEBS Letters

Friedler, Assaf³  Blumenzweig, Immanuel¹  Baraz, Lea¹  Chen, Nissim¹  Gilon, Chaim³  Steinitz, Michael²  Kotler, Moshe¹  Nussinuv, Orna¹ 

[1] Department of Molecular Genetics, The Hebrew University-Hadassah Medical School, Jerusalem 91010, Israel;Department of Pathology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel;Department of Organic Chemistry, The Hebrew University, Jerusalem, Israel

关键词: HIV-1 protease;    Protease regulation;    Peptide;    Vif;    Human immunodeficiency virus type 1;    Acquired immunodeficiency syndrome;   

DOI  :  10.1016/S0014-5793(98)01602-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Human immunodeficiency virus type 1 (HIV-1) Vif protein is required for productive HIV-1 infection of peripheral blood lymphocytes and macrophages in cell culture and for pathogenesis in the SCID-hu mouse model of HIV-1 infection. Vif inhibits the viral protease (PR)-dependent autoprocessing of truncated HIV-1 Gag-Pol precursors expressed in bacterial cells and efficiently inhibits the PR-mediated hydrolysis of peptides in cell-free systems. The obstructive activity of Vif has been assigned to the 92 amino acids residing at its N′-terminus (N-Vif). To determine the minimal Vif sequence required to inhibit PR, we synthesized overlapping peptides derived from N-Vif. These peptides were then assessed, using two in vitro and two in vivo systems: (i) inhibition of purified PR, (ii) binding of PR, (iii) inhibition of the autoprocessing of the Gag-Pol polyprotein expressed by a vaccinia virus vector, and (iv) inhibition of mature virus production in human cells. The peptides derived from two regions of N-Vif encompassing residues Tyr-30–Val-65 and Asp-78–Val-98, inhibited PR activity in both the in vitro and the in vivo assays. Thus, these peptides can be used as lead compounds to design new PR inhibitors.

【 授权许可】

Unknown