TARGET-CELLS DURING EARLY SIV ENCEPHALOPATHY

Early encephalopathy was studied in rhesus macaques in the first month following intravenous (i.v.) infection with SIV-mac-251. Histopathological analysis of brain tissues showed slight gliosis, associated with perivascular infiltrates and occasional glial nodules. Immunophenotyping of brain tissue showed microgliosis with expression of MHC class 11 molecule and macrophage infiltration associated with a few lymphocytes. At the early stage of infection, most infected cells were perivascular, suggesting that infiltrating cells are the main route of entry of the virus into the brain. Using combined immunochemistry and in situ hybridization, it was shown that these infected perivascular cells were mostly macrophages. Later, SIV infected a limited number of cells expressing the same CD68 monocyte/macrophage/microglia marker. Using different genome probes, hypotheses concerning SIV RNA expression during early brain infection were tested. It was shown that the latent brain infection was not due to a complete transcription block, but rather to productive replication of SIV at a low level in a small number of target cells in the brain. Injection of SIV by the intracerebral (i.c.) route induced the same slight encephalitis as observed in i.v. inoculated animals. The very small number of infected cells found around the site of i.c. inoculation suggests that resident microglia are poorly susceptible to infection by SIV.