Inhibition of endogenous reverse transcription of human and nonhuman primate lentiviruses: potential for development of lentivirucides
| Autor: | Roger J. Pomerantz, Ketti E. Mehlman, Hui Zhang, Edward Acheampong, Chune Zhang, Elias G. Argyris, Giuseppe Nunnari, Geethanjali Dornadula |
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| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
NNRTI
Sexual transmission Transcription Genetic T cell T-Lymphocytes viruses Endogeny Biology Antiviral Agents Article RT Zidovudine Virucide Virology medicine Disease Transmission Infectious Humans Thymine Nucleotides Nevirapine Cells Cultured Infectivity virus diseases Reverse transcriptase medicine.anatomical_structure SIV Cell culture NERT NRTI Lentivirus Infections HIV-1 Reverse Transcriptase Inhibitors Simian Immunodeficiency Virus medicine.drug Dideoxynucleotides |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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