AMPHIPATHIC DOMAINS IN THE C-TERMINUS OF THE TRANSMEMBRANE PROTEIN (GP41) PERMEABILIZE HIV-1 VIRIONS - A MOLECULAR MECHANISM UNDERLYING NATURAL ENDOGENOUS REVERSE TRANSCRIPTION

Reverse transcription of HIV-1, without detergent or amphipathic pepti de-induced permeability of the viral envelope, has been demonstrated t o occur in the intact HIV-1 virion. In this report, we demonstrate tha t the amphipathic domains in the C terminus of the transmembrane glyco protein (gp41) account for the natural permeability of the HIV-1 envel ope to deoxyribonucleoside triphosphates, the substrates for DNA polym erization, In addition, nonphysiological deoxyribonucleoside triphosph ates, such as 3'-azido-3'-deoxythymidine 5'-triphosphate and 3'-deoxyt hymidine 5'triphosphate, can also penetrate the viral envelope, incorp orate into, and irreversibly terminate reverse transcripts, As a resul t, viral infectivity is potently inhibited, Since the lentiviral envel ope with these newly demonstrated characteristics can serve as a deliv ery pathway for anti-reverse transcription agents, we propose a unique strategy to prevent HIV-1 inter- and, possibly, intrahost transmissio n.