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PubMed · 10534141

Nitric oxide modulates HIV-1 replication.

J B Mannick·J S Stamler·E Teng·N Simpson·J Lawrence·J Jordan·R W Finberg
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Abstract

Although nitric oxide (NO) production is increased in HIV-1-infected patients, and NO is known to inhibit the replication of several viruses, very little is known about the effects of NO on HIV-1 replication. In the present studies, we find that S-nitrosothiols (RSNOs), a class of NO donor compounds present in the human circulatory system, inhibit HIV-1 replication in acutely infected human peripheral blood mononuclear cells (PBMCs) and have an additive inhibitory effect on HIV-1 replication in combination with 3'-azido-3'-deoxythymidylate (AZT). RSNOs inhibit HIV-1 replication in acutely infected PBMCs at a step in the viral replicative cycle after reverse transcription, but before or during viral protein expression through a cGMP-independent mechanism. In the latently infected U1 cell line, NO donor compounds and intracellular NO production stimulate HIV-1 reactivation. These studies suggest that NO both inhibits HIV-1 replication in acutely infected cells and stimulates HIV-1 reactivation in chronically infected cells. Thus, NO may have a physiologic role in HIV-1 replication, and NO donor compounds, which have been used for decades in the treatment of coronary artery disease with limited toxicity, might be useful in the treatment of HIV-1 disease by inhibiting acute infection, reactivating latent virus, or both.

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AdultAnti-HIV AgentsCell LineCells, CulturedCyclic GMPDNA, ViralDose-Response Relationship, DrugDrug SynergismEnzyme InhibitorsHIV-1HumansLeukocytes, MononuclearMercaptoethanolNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitroso CompoundsPenicillamineS-Nitroso-N-AcetylpenicillamineS-NitrosothiolsTranscription, GeneticViral ProteinsVirus ReplicationZidovudineomega-N-MethylarginineJournal Article

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J B Mannick, J S Stamler, E Teng, N Simpson, J Lawrence, J Jordan, R W Finberg. 1999-09-01. Nitric oxide modulates HIV-1 replication.. https://doi.org/10.1097/00042560-199909010-00001

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