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Efavirenz enhances the proteolytic processing of an HIV‐1 pol polyprotein precursor and reverse transcriptase homodimer formation
Author(s) -
Tachedjian Gilda,
Moore Katie L.,
Goff Stephen P.,
Sluis-Cremer Nicolas
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.099
Subject(s) - efavirenz , reverse transcriptase , nevirapine , nucleotidyltransferase , chemistry , processivity , virology , biology , human immunodeficiency virus (hiv) , biochemistry , enzyme , rna , polymerase , gene , viral load , antiretroviral therapy
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.