The human immunodeficiency virus type 1 (HIV-1) auxiliary gene vif is essential for virus propagation in peripheral blood lymphocytes, macrophages, and in some T-cell lines. Previously, it was demonstrated that Vif inhibits the autoprocessing of truncated HIV-1 Gag-Pol polyproteins expressed in bacterial cells, and that purified recombinant Vif and Vif-derived peptides inhibit and bind HIV-1 protease (PR). Here we show that Vif interacts with the N-terminal region of HIV-1 PR, and demonstrate that peptide derived from the N-terminal region of PR abrogates Vif function in non-permissive cells. Specifically, we show that (i) Vif protein binds HIV-1 PR, but not covalently linked tethered PR-PR; (ii) the four amino acids residing at the N terminus of HIV-1 PR are essential for Vif/PR interaction; (iii) synthetic peptide derived from the N terminus of HIV-1 PR inhibits Vif/PR binding; and (iv) this peptide inhibits the propagation of HIV-1 in restrictive cells. Based on these data, we suggest that Vif interacts with the dimerization sites of the viral protease, and that peptide residing at the N terminus of PR abrogates Vif function(s).
Bibliographical noteFunding Information:
This work was carried out in the Peter A. Krueger Laboratory with the generous support of Nancy and Lawrence Glick, and Pat and Marvin Weiss. We thank Dr. D. Gabuzda for providing the Vif-expressing vector and polyclonal (anti-) Vif serum and Dr. K. Strebel for providing pcDNA-APO3G. Anti-CA was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH. This work was supported in part by The Israel Science Foundation, and the Israel Ministry of Health. We thank Mrs. S. Amir for editing this manuscript.
- HIV-1 protease
- Synthetic peptides