ISOLATION AND CHARACTERIZATION OF A NEUROPATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS DERIVED FROM A SOOTY MANGABEY

Transfusion of blood from a simian immunodeficiency virus (SIV)- and s imian T-cell lymphotropic virus-infected sooty mangabey (designated FG b) to rhesus and pig-tailed macaques resulted in the development of ne urologic disease in addition to AIDS. To investigate the role of SIV i n neurologic disease, virus was isolated from a lymph node of a pig-ta iled macaque (designated PGm) and the cerebrospinal fluid of a rhesus macaque (designated ROn2) and passaged to additional macaques. SIV-rel ated neuropathogenic effects were observed in 100% of the pig-tailed m acaques inoculated with either virus. Lesions in these animals include d extensive formation of SIV RNA-positive giant cells in the brain par enchyma and meninges. Based upon morphology, the majority of infected cells in both lymphoid and brain tissue appeared to be of macrophage l ineage. The virus isolates replicated very well in pig-tailed and rhes us macaque peripheral blood mononuclear cells (PBMC) with rapid kineti cs. Differential replicative abilities were observed in both PBMC and macrophage populations, with viruses growing to higher titers in pig-t ailed macaque cells than in rhesus macaque cells. An infectious molecu lar clone of virus derived from the isolate from macaque PGm (PGm5.3) was generated and was shown to have in vitro replication characteristi cs similar to those of the uncloned virus stock. While molecular analy ses of this virus revealed its similarity to SIV isolates from sooty m angabeys, significant amino acid differences in Env and Nef were obser ved. This virus should provide an excellent system for investigating t he mechanism of lentivirus-induced neurologic disease.