High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis

AIDS dementia and encephalitis are complications of AIDS occurring most fre quently in patients who are immunosuppressed, The simian immunodeficiency v irus (SIV) model used in this study was designed to reproducibly induce,AID S in macaques in order to examine the effects of a neurovirulent virus in t his context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moder ate to severe encephalitis within 6 months of inoculation. Viral load in pl asma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine th e relationship of systemic and central nervous system (CNS) viral replicati on to the development of encephalitis. In all animals, plasma viral load pe aked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In c ontrast, persistent high levels of CSF viral RNA after the acute phase of i nfection correlated with the development of encephalitis. Although high lev els of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA a nd antigen in the brain correlated with the severity of the CNS lesions. Th e single animal in this group that did not have CNS lesions had no detectab le viral RNA in any of the regions of the brain. The results substantiate t he use of CSF viral load measurements in the postacute phase of SIV infecti on as a marker for encephalitis and CNS viral replication.