4th Conference on Retroviruses and Opportunistic Infections
Washington, DC - January 22-26, 1997
Amphipathic domains in the C-terminus of the transmembrane protein (gp41) permeabilize HIV-1 virions: a molecular mechanism underlying natural endogenous reverse transcription.
Zhang H, Dornadula G, Alur P, Laughlin MA, Pomerantz RJ; Dorrance H. Hamilton Laboratories, Center for Human Virology, Thomas Jefferson University, Philadelphia, PA.
Reverse transcription of human immunodeficiency virus type I (HIV-1), without detergent or amphipathic peptide-induced permeability of the viral envelope, has been demonstrated to occur in the intact HIV-1 virion. In this report, we demonstrate that the amphipathic domains in the C-terminus of the transmembrane glycoprotein (gp41) account for the natural permeability of the HIV-1 envelope to deoxyribonucleoside triphosphates (dNTPs), the substrates for DNA polymerization. In addition, non-physiological deoxyribonucleoside triphosphates, such as 3'-azido-3'-deoxythymidine 5-triphosphate (AZTTP) and 2', 3'-dideoxythymidine 5'-triphosphate (ddTTP), can also penetrate the viral envelope, incorporate into and irreversibly terminate reverse transcripts. As a result, viral infectivity is potently inhibited. Since the lentiviral envelope with these newly demonstrated characteristics can serve as a delivery pathway for anti-reverse transcription agents, we propose a unique strategy to prevent HIV-1 inter- and possibly, intra-host transmission. (Proceedings of the Natural Academy of Sciences, USA, In Press).
Keywords: AEGIS, Virion, HIV-1, Transcription, Genetic, HIV Envelope Protein gp41, HIV-1 Reverse Transcriptase, Thymine Nucleotides, Gene Products, vif, Zidovudine, Gene Products, nef, Reverse Transcriptase Inhibitors, Gene Products, gag, HIV Envelope Protein gp160, Anti-HIV Agents, Proteins, Gene Products, env, 2',3'-dideoxythymidine triphosphate, 3'-azido-3'-deoxythymidine 5'-triphosphate, thymidine 5'-triphosphate, Human, genetics, AIDS
