IMPACT OF VARIOUS SIMIAN IMMUNODEFICIENCY VIRUS VARIANTS ON INDUCTIONAND NATURE OF NEUROPATHOLOGY IN MACAQUES

To investigate the possible influence of virus tropism on SIV-induced neuropathogenesis, macaques were infected with molecularly cloned SIVm ac239 which replicates poorly in cultured macrophages, with SIVmac251/ 32H which is a macrophage-tropic biologic clone, and with SIVmac251/MP BMC which is an early passage of 32H with enhanced replication compete nce in macrophages. We found that inflammatory as well as neuropatholo gic changes were identical in all clinically affected animals, irrespe ctive of the in vitro tropism of the inocula. Moribund animals exhibit ed SIV encephalitis characterized by overt infection of macrophages/mi croglia inside the CNS parenchyma. Additionally, neuropathology of mor ibund animals was characterized by extraparenchymal immunopathology (m eninges, perivascular space, choroid plexus stroma) and subtle white m atter degeneration with glial changes, often associated with infected macrophages in situ (except in leukoencephalopathy). However, in anima ls inoculated with the lymphocyte-tropic and enhanced macrophage-tropi c inocula, microglia but not blood-derived macrophages were the primar y cells infected. Altogether, our results underline the significance o f macrophage infection for the development of SIV encephalitis, and su ggest that SIVmac239 either undergoes a change in cell tropism in vivo that results in the ability to replicate in macrophages, or else macr ophages became more permissive to infection by this virus in the termi nal stage of immunosuppressive disease.