Abrogation of Vif function by peptide derived from the N-terminal region of the human immunodeficiency virus type 1 (HIV-1) protease.
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).
Hutoran
Marina
M
Department of Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Britan
Elena
E
Baraz
Lea
L
Blumenzweig
Immanuel
I
Steinitz
Michael
M
Kotler
Moshe
M
D001483:Base Sequence; D017931:DNA Primers; D016346:Gene Products, vif / Q000037:antagonists & inhibitors* / Q000502:physiology*; D016333:HIV Protease / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D010446:Peptide Fragments / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus
D017931:DNA Primers; D016346:Gene Products, vif; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D001616:beta-Galactosidase; D016333:HIV Protease