Expression of IL-18 by SIV does not modify the outcome of the antiviral immune response

Interleukin 18 (IL-18) is a proinflammatory cytokine expressed by several cell types, including activated dendritic cells and macrophages, that acts in synergy with IL-12 as an important amplifying factor for IFN-γ production and Th1 development. To study the immunological and virological effects of IL-18 expression in the context of a lentiviral infection, we inoculated rhesus macaques with a high dose of replication-competent simian immunodeficiency virus (SIV) vectors carrying the rhesus IL-18 gene in the sense (SIV_IL-18) or antisense (SIV_FIGI) orientation. Both vectors behaved as attenuated viruses, resulting in low viral loads, induction of low and transient levels of inflammatory cytokines, no CD4⁺ T cell depletion, and mild activation of T lymphocytes. Although IL-18-expressing virus could be isolated from some SIV_IL18-infected macaques for 12 weeks postinfection, the anti-SIV humoral and cellular immune responses of macaques inoculated with SIV_IL18 and SIV_FIGI were similar to each other, with the exception of an early IFN-γ response in animals infected with SIV_IL18. In summary, expression of IL-18 during the acute phase of SIV infection does not increase viral replication or influence the outcome of the antiviral immune response.