Central nervous system immune activation and the neuropathogenesis of pediatric acquired immune deficiency syndrome in the simian immunodeficiency virus-infected rhesus macaque (Macaca mulatta)
Date of Completion
Agriculture, Animal Pathology|Health Sciences, Pathology|Biology, Veterinary Science
Neonatal Human Immunodeficiency Virus (HIV) infection results in a higher incidence of clinical neurologic disease than is seen in adults, but histopathologic findings indicate there are fewer inflammatory foci in the brain with pediatric AIDS. Classical lesions of HIV encephalitis are not seen in pediatric AIDS despite higher viral loads. Neonatal rhesus monkeys infected immediately postpartum with Simian Immunodeficiency Virus (SIV) have been used to model HIV infection of infants. As with the adult SIV infected rhesus macaque model of HIV infection, neonatal macaques infected with SIV show gross and histologic changes that closely match the neuropathology of HIV infection. Paradoxically, viral loads in the brains of animals infected with SIV as neonates are markedly lower as compared to SIV-infected adults despite comparable peripheral viral loads in both age groups. The mechanism(s) responsible for the attenuation of CNS inflammation in pediatric patients, both human and monkey, are unclear. These studies show that there are increased immunoreactive microglia, but not macroglia or lymphocytes in the brain with early pediatric SIV infection. Pediatric SIV infection results in rapid sustained functional maturation of GLUT-1 on brain endothelial cells, but does not alter tight junction integrity through terminal AIDS. Two complementary model systems were developed to study immune activation with pediatric AIDS. Post-transfusion Graft vs. Host Response/pediatric SIV infection increases cytotoxic T lymphocyte (CTL) responses and supports activated memory helper T cells. CD8-depletion/pediatric SIV infection abrogates CTL for at least 21 days and supports activated memory helper T cells. Age-dependent systemic immune factors and structure/function changes in the blood-brain barrier appear to underlie the “immunosuppression of immaturity” that leads to differences in pathology with pediatric AIDS. ^
Bowenkamp, Kathryn Elizabeth, "Central nervous system immune activation and the neuropathogenesis of pediatric acquired immune deficiency syndrome in the simian immunodeficiency virus-infected rhesus macaque (Macaca mulatta)" (2002). Doctoral Dissertations. AAI3076691.