title: Efavirenz enhances the proteolytic processing of an HIV-1 pol polyprotein precursor and reverse transcriptase homodimer formation.
abstract: The non-nucleoside reverse transcriptase inhibitor, efavirenz (EFV), is a potent enhancer of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) p66/p51 heterodimerization. While the mechanism of RT heterodimer formation in HIV-1 infected cells is not completely understood, it has been speculated that Gag-Pol/Gag-Pol and/or RT homodimer interactions may represent important intermediates in the pathway. To elucidate whether EFV impacts on these interactions, we have evaluated the effects of this drug on RT homodimer interactions and HIV-1 Gag-Pol processing. EFV, but not nevirapine, significantly enhanced RT p66/p66 and p51/p51 homodimer interactions and accelerated the proteolytic cleavage of a model HIV-1 Pol polyprotein precursor expressed in bacteria. These data suggest that potent mediators of RT dimerization might interfere with the late-stages of viral replication.
authors.affiliation: Molecular Interactions Group, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Road, Melbourne, Vic. 3004, Australia. gildat@burnet.edu.au
authors.forename: Gilda
authors.initials: G
authors.lastname: Tachedjian
authors.forename: Katie L
authors.initials: KL
authors.lastname: Moore
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology*; D048588:Benzoxazines; D003521:Cyclopropanes; D019281:Dimerization; D015685:Fusion Proteins, gag-pol / Q000378:metabolism*; D054303:HIV Reverse Transcriptase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019829:Nevirapine / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology*; D011498:Protein Precursors / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D020798:Two-Hybrid System Techniques
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015685:Fusion Proteins, gag-pol; D010078:Oxazines; D011498:Protein Precursors; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; C098320:efavirenz