Role of nitric oxide in HIV-1 infection: friend or foe?
Nitric oxide (NO) is an important biologically active molecule that plays a key part in host defence against bacteria, protozoa, and tumour cells. NO has antiviral effects against several DNA viruses, such as murine poxvirus, herpes simplex virus, and Epstein-Barr virus, and some RNA viruses, such as coxsackievirus. In several studies, in vitro and in vivo, overproduction of NO has been noted in the presence of HIV-1 infection. Furthermore, increased NO production may contribute directly to the pathogenesis of HIV-1-associated dementia. The mechanisms of virus infection mediated by NO may be related to: direct antiviral effects of NO; impairment of antiviral defence mediated by T-helper-1 immune response by suppressing T-helper-1 functions; NO-induced cytotoxic effects by oxidative injury with cellular and organ dysfunctions; and NO-induced oxidative stress leading to rapid viral evolution with productions of drug-resistant and immunologically tolerant mutants. By contrast, there is some evidence of NO activity--directly, indirectly, or both--decreasing or blocking HIV-1 replication, through inhibition of viral enzymes, such as reverse transcriptase, protease, or cellular nuclear transcription factor (NF-kappa B) and long-terminal repeat-driven transcription. Therefore, although NO surely plays an important part in HIV-1 infection, that role is sometimes helpful and other times damaging to the host. Future challenges are to learn more about the beneficial and harmful effects of NO in HIV-1 infection, and how to selectively inhibit excessive NO production or to use NO-releasing drugs to decrease viral replication. This review discusses the role of NO in the pathogenesis of HIV-1 infection, inasmuch as its role against HIV-1 is unequivocal in inhibiting or increasing viral replication.
Torre
Donato
D
Department of Infectious Diseases, Regional Hospital and Macchi Foundation, Varese, Italy. eiwle@tin.it
Pugliese
Agostino
A
Speranza
Filippo
F
D015526:AIDS Dementia Complex / Q000209:etiology*; D000328:Adult; D002648:Child; D015658:HIV Infections / Q000209:etiology / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D014779:Virus Replication
D009569:Nitric Oxide