PATHOGENESIS OF LYMPHOCYTE-TROPIC AND MACROPHAGE TROPIC SIVMAC INFECTION IN THE BRAIN

SIV(mac)239 replicates productivity in activated CD4+ T lymphocytes, b ut inefficiently in macrophages from rhesus macrophages. Inoculation o f the virus into animals results in an acute, highly productive burst of virus replication in activated T lymphocytes in lymphoid tissues an d infected cells invade the central nervous system (CNS). This phase l asts a few weeks and is eventually followed by development of immunosu ppression of different degrees of severity, opportunistic infections, and tumors related to the loss of T lymphocytes. On rare occasions, in fected immunosuppressed animals develop encephalitis and/or interstiti al pneumonia, syndromes that are associated with selection of mutant v iruses that replicate efficiently in macrophages of these tissues. Usu ally, however, brains of animals dying with AIDS caused by SIV(mac)239 appear histologically normal. Is the brain infected with virus? We re port here on a macaque dying with AIDS, a neuroinvasive tumor and inte rstitial pneumonia associated with macrophage-tropic virus. Except for focal infiltration of tumor cells, the brain was normal histologicall y. We examined the virus and viral DNA from different tissues and foun d that lymphocytes but not macrophages from lymph nodes and spleen yie lded virus, whereas macrophages-but not lymphocytes from the lung prod uced virus. No virus was recovered from the brain but small amounts of viral p27 were present in the brain homogenate. Viral sequences were present in the brain as determined by PCR from tissue DNA. Comparison showed that the viral sequences in the brain closely resembled those f rom the spleen. Presumably, the virus caused a minimally productive in fection detectable by production of small amounts of p27, but was not accompanied by any histopathological changes. It is unclear why the ma crophage-tropic virus in the lung failed to 'take-off' in the brain of this animal. To determine whether this virus had encephalitic potenti al, we inoculated the lung homogenate containing cell-free, macrophage tropic virus into a young pigtail macaque, a species known to be sens itive to primate lentiviral infections. This animal developed severe e ncephalitis 10 weeks later. Virus from the brain was very similar to t he inoculum virus, proving its encephalitic potential. Possible reason s for the differences in neurovirulence of this virus between the two animals remain speculative.