Simian immunodeficiency virus encephalitis: Analysis of envelope sequences from individual brain multinucleated giant cells and tissue samples

Simian immunodeficiency virus (SIV)-infected macaques develop an encephalitis (SIVE) that is pathologically virtually indistinguishable from that associated with HIV infection, with multinucleated giant cells (MNGCs) being the principal histopathological manifestation. To dissect SIV variants responsible for MNGC development, we examined the relationships between env sequences transcribed in individual MNGCs and those from genomic DNA of brain and spleen tissues. The brain-specific variant found in all brain clones was dominant among the clones from MNGCs, suggesting a role in the formation of giant cells. Furthermore, two additional minor groups of sequences were present in MNGCs. One group consisted of sequences closely related to those from spleen, indicating recent and probably multiple episodes of neuroinvasion. The second group represented clones similar or identical to the initial inoculum. The survival of archival sequences and their activation presumably by the fusion of productively and quiescently infected macrophages/microglia identify the central nervous system as a possible anatomical reservoir for latent infection.