Increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis

Objectives: Widespread dendritic injury may be one mechanism involved in th e neurologic impairment that occurs in HIV-1 infection. The objectives of t his study were to quantitate the extent of dendritic injury in a primate mo del of central nervous system (CNS) infection, investigate the role of nitr ic oxide (NO) as a mediator of neuropathologic changes, and evaluate the re lation of these changes to cognitive and motor function. Study Design/Methods: Cognitive and motor function was assessed in rhesus m acaque monkeys infected with simian immunodeficiency virus (SN). In situ hy bridization, immunohistochemistry, and quantitative image analysis were emp loyed to assess the relations among productive infection, NO synthase (iNOS ), and dendritic injury. Results: Productive infection of cells of the macrophage lineage in CNS is associated with inflammation, increased expression of iNOS, and dendritic i njury. The tests of cognitive and motor function employed were abnormal in both animals that had evidence of productive infection and those that did n ot. Conclusions: Increased NO accompanying productive infection and encephaliti s may be one cause of neuronal injury in lentivirus infections of the CNS. Extension of tests of cognitive and motor function to late-stage AIDS in rh esus monkeys is needed to assess the potential role of NO-induced dendritic damage in lentiviral encephalopathy/AIDS dementia complex.