Nitric oxide synthesis during acute SIVmac251 infection of macaques

Summary During HIV1 infection, nitric oxide (NO) could significantly contribute to immune dysregulation by its multiple effects on the modulation of the host immune response. The in vivo regulation of NO production is attributable to several nitric oxide synthases, one of which is a cytokine-inducible enzyme (iNOS). In vitro experiments suggest that iNOS expression in macrophages may be directly modulated by HIV infection. Acute infection of macaques with a pathogenic strain of the simian immunodeficiency virus (SIV) represents a relevant animal model for the in vivo study of the relationships between iNOS expression and lentiviral replication. Indeed, acute infection in this model is characterized by high rates of viral replication associated with early cytokine dysregulations, in the absence of opportunistic infection. In our experiment, two cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac251, and iNOS gene expression was investigated ex vivo during acute infection in mononuclear cells obtained from bronchoalveolar lavage (BALMCs). An enhancement of this gene expression was observed as early as the second week of infection, at the time of peak of systemic viraemia, and increased until day 31 p.i. This overexpression was concomitant with a marked linear increase in IFNγ expression in BALMCs. At the time of systemic viral load peak, the production of NO in plasma of these two monkeys was evidenced by the detection of large amounts of nitrate.