Nitric oxide modulates HIV-1 replication

Although nitric oxide (NO) production is increased in HIV-1-infected patien ts, and NO is known to inhibit the replication of several viruses, very lit tle is known about the effects of NO on HIV-1 replication. In the present s tudies, we find that S-nitrosothiols (RSNOs), a class of NO donor compounds present in the human circulatory system, inhibit HIV-1 replication in acut ely infected human peripheral blood mononuclear cells (PBMCs) and have an a dditive inhibitory effect on HIV-1 replication in combination with 3'-azido -3'-deoxythymidylate (AZT). RSNOs inhibit HIV-1 replication in acutely infe cted PBMCs at a step in the viral replicative cycle after reverse transcrip tion, but before or during viral protein expression through a cGMP-independ ent mechanism. In the latently infected U1 cell line, NO donor compounds an d intracellular NO production stimulate HIV-1 reactivation. These studies s uggest that NO both inhibits HIV-1 replication in acutely infected cells an d stimulates HIV-1 reactivation in chronically infected cells. Thus, NO may have a physiologic role in HIV-1 replication, and NO donor compounds, whic h have been used for decades in the treatment of coronary artery disease wi th limited toxicity, might be useful in the treatment of HIV-1 disease by i nhibiting acute infection, reactivating latent virus, or both.