SERIAL PASSAGE OF MICROGLIAL SIV RESULTS IN SELECTION OF HOMOGENEOUS ENV QUASI-SPECIES IN THE BRAIN

The pathogenic effects of HIV include infection of the central nervous system (CNS) which can result in cognitive and motor dysfunction. Sim ian immunodeficiency virus (SIV) infection of rhesus macaques provides an excellent model of HIV-induced disease. We have achieved a reprodu cible infection of the CNS using a stock of virus obtained by serial p assage of microglia-associated SIV. Since the envelope genes of both H IV and SIV encode determinants important in viral pathogenesis, and th e variability inherent in these viruses provides a molecular footprint of viral quasispecies, we analyzed the viral env sequences resulting from this serial passage. SIV env sequences were analyzed by direct PC R amplification of DNA isolated from microglia from infected animals. Nucleotide sequence comparison reveals that serial passage of microgli a-associated SIV resulted in divergence from the donor stock of virus. Furthermore, an enrichment of unique env quasispecies which is mainta ined through the serial passage was found in the diseased brains. (C) 1995 Academic Press, Inc.