FEBS Letters | |
Human immunodeficiency virus type 1 Vif‐derived peptides inhibit the viral protease and arrest virus production | |
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
【 预 览 】
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