Intracerebral infusion of TNF-alpha and IL-6 failed to activate latent SIV infection in the brains of macaques inoculated with macrophage-tropic neuroadapted SIVmac.

Lymphocyte-tropic (L-tropic) SIVmac predictably causes immunosuppression and AIDS in rhesus macaques. SIV encephalitis, on the other hand, is caused mainly by macrophage-tropic (M-tropic) SIVmac. We have previously described the derivation of M-tropic, neuroadapted SIVmac from molecularly cloned, L-tropic SIVmac239. In this report we show that inoculation of four macaques with neuroadapted virus resulted in L-tropic SIVmac-related diseases in all four but neurological disease in only two of the four animals. Because cocultivation of infected macrophages with CD4+ lymphocytes results in production of tumor necrosis factor alpha and interleukin-6, we asked whether infiltration of supernatant fluids containing these cytokines into the brains of macaques infected with neuroadapted virus would enhance the development of neurological disease. These procedures failed to promote productive virus replication in the brain. Thus, although different degrees of immunosuppression and AIDS could be induced predictably with L-tropic virus, induction of neurological disease was not predictable even when animals were inoculated with neuroadapted M-tropic virus and inflammatory cytokines were infiltrated into the brains of these animals.