Inhibition of endogenous reverse transcription of human and nonhuman primate lentiviruses: potential for development of lentivirucides.
In the current study, we extended our previous works on natural endogenous reverse transcription (NERT) and further examined its potential as a virucide molecular target in sexual transmission of primate lentiviruses. HIV-1 and SIV virions were pretreated with select nucleoside (NRTIs) and nonnucleoside RT inhibitors (NNRTIs), either alone or in combination with NERT-stimulating substances. The effects of these antiretrovirals on virion inactivation were analyzed in human T cell lines and primary cell cultures. Pretreatment of HIV-1 virions with physiologic NERT-stimulants and 3'-azido-3'-deoxythymidine 5'-triphosphate (AZT-TP) or nevirapine potently inactivated cell-free HIV-1 virions and resulted in strong inhibition of the viral infectivity. Pretreatment of chimeric SHIV-RT virions with NERT-stimulating cocktail and select antiretrovirals also resulted in virion inactivation and inhibition of viral infectivity in T cell lines. Our findings demonstrate the potential clinical utility of approaches based on inhibiting NERT in sexual transmission of HIV-1, through the development of effective anti-HIV-1 microbicides, such as NRTIs and NNRTIs.
Argyris
Elias G
EG
Center for Human Virology, Division of Infectious Diseases, Department of Medicine, Thomas Jefferson University, 1020 Locust Street, Suite 334, Philadelphia, PA 19107, USA.
Dornadula
Geethanjali
G
Nunnari
Giuseppe
G
Acheampong
Edward
E
Zhang
Chune
C
Mehlman
Ketti
K
Pomerantz
Roger J
RJ
Zhang
Hui
H
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D054306:Dideoxynucleotides; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016180:Lentivirus Infections / Q000517:prevention & control / Q000635:transmission; D019829:Nevirapine / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes; D013942:Thymine Nucleotides / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000998:Antiviral Agents; D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D019829:Nevirapine