Human immunodeficiency virus type 1 Vif binds the viral protease by interaction with its N-terminal region.
The vif gene, one of the six auxiliary genes of human immunodeficiency virus (HIV), is essential for virus propagation in peripheral blood lymphocytes and macrophages and in certain T-cell lines. Previously, it was demonstrated that Vif inhibits the autoprocessing of truncated HIV type 1 (HIV-1) Gag-Pol polyproteins expressed in bacterial cells, as well as the protease-mediated cleavage of synthetic peptides in vitro. Peptides derived from the aa 78-98 region in the Vif molecule specifically inhibit and bind the HIV-1 protease in vitro and arrest the production of infectious viruses in HIV-1-infected cells. This study demonstrates that (i) purified recombinant Vif protein and HIV-1 but not avian sarcoma leukaemia virus protease specifically bind each other and (ii) the interaction between these two proteins takes place at the N terminus of the protease (aa 1-9) and the central part of Vif (aa 78-98). The data presented in this report suggest a model in which Vif interacts with the dimerization sites of the viral protease.
Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel1.
Lea
L
Baraz
Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel1.
Marina
M
Hutoran
Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel1.
Immanuel
I
Blumenzweig
Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel1.
Mark
M
Katzenellenbogen
Department of Organic Chemistry, The Hebrew University, Givat Ram, Jerusalem 91904, Israel2.
Assaf
A
Friedler
Department of Organic Chemistry, The Hebrew University, Givat Ram, Jerusalem 91904, Israel2.
Chaim
C
Gilon
Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel1.
Michael
M
Steinitz
Experimental Pathology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel1.
Moshe
M
Kotler
D001665:Binding Sites; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D016346:Gene Products, vif / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D017320:HIV Protease Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D016333:HIV Protease