Serial Passage of Microglial SIV Results in Selection of Homogeneous env Quasispecies in the Brain

The pathogenic effects of HIV include infection of the central nervous system (CNS) which can result in cognitive and motor dysfunction. Simian immunodeficiency virus (SIV) infection of rhesus macaques provides an excellent model of HIV-induced disease. We have achieved a reproducible infection of the CNS using a stock of virus obtained by serial passage of microglia-associated SIV. Since the envelope genes of both HIV and SIV encode determinants important in viral pathogenesis, and the 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 PCR amplification of DNA isolated from microglia from infected animals. Nucleotide sequence comparison reveals that serial passage of microglia-associated SIV resulted in divergence from the donor stock of virus. Furthermore, an enrichment of unique env quasispecies which is maintained through the serial passage was found in the diseased brains.