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

Lea Baraz, Assaf Friedler, Immanuel Blumenzweig, Orna Nussinuv, Nissim Chen, Michael Steinitz, Chaim Gilon, Moshe Kotler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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. Copyright (C) 1998 Federation of European Biochemical Societies.

Original languageAmerican English
Pages (from-to)419-426
Number of pages8
JournalFEBS Letters
Volume441
Issue number3
DOIs
StatePublished - 28 Dec 1998

Keywords

  • Acquired immunodeficiency syndrome
  • HIV-1 protease
  • Human immunodeficiency virus type 1
  • Peptide
  • Protease regulation
  • Vif

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