Neuropathogenesis of chimeric simian human immunodeficiency virus infection in rhesus macaques

Comparative studies were performed to determine the neuropathogenesis of in fection in macaques with simian human immunodeficiency virus (SHIV)89.6P an d SHIVKU. Both viruses utilize the CD4 receptor and CXCR4 co-receptor. Howe ver, in addition, SHIV89.6P uses the CCR5 co-receptor. Both agents are dual tropic for CD4(+) T cells and blood-derived macrophages of rhesus macaques . Following inoculation into macaques, both caused rapid elimination of CD4 (+) T cells but they varied greatly in mechanisms of neuropathogenesis. Two animals infected with SHIV89.6P developed typical lentiviral encephalitis in which multinucleated giant cell formation, nodular accumulations of micr oglial cells, activated macrophages and astrocytes, and perivascular accumu lations of mononuclear cells were present in the brain. Many of the macroph ages in these lesions contained viral RNA. Three macaques infected with SHI VKU and killed on days 6, 11 and 18, respectively, developed a slowly progr essive infection in the CNS but macrophages were not productively infected and there were no pathological changes in the brain. Two other animals infe cted with this virus and killed several months later showed minimal infecti on in the brain even though one of the two developed encephalitis of unknow n etiology. The basic difference in the mechanisms of neuropathogenesis by the two viruses may be related to co-receptor usage. SHIV89.6P, in utilizin g the CCR5 co-receptor, caused neuropathogenic effects that are similar to other neurovirulent primate lentiviruses.