Increased expression of nitric oxide synthase and dendritic injury in simian immunodeficiency virus encephalitis.
OBJECTIVE
Widespread dendritic injury may be one mechanism involved in the neurologic impairment that occurs in HIV-1 infection. The objectives of this study were to quantitate the extent of dendritic injury in a primate model of central nervous system (CNS) infection, investigate the role of nitric oxide (NO) as a mediator of neuropathologic changes, and evaluate the relation of these changes to cognitive and motor function.


METHODS
Cognitive and motor function was assessed in rhesus macaque monkeys infected with simian immunodeficiency virus (SIV). In situ hybridization, immunohistochemistry, and quantitative image analysis were employed 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 injury. The tests of cognitive and motor function employed were abnormal in both animals that had evidence of productive infection and those that did not.


CONCLUSIONS
Increased NO accompanying productive infection and encephalitis 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 rhesus monkeys is needed to assess the potential role of NO-induced dendritic damage in lentiviral encephalopathy/AIDS dementia complex.
Li
Q
Q
Department of Microbiology, University of Minnesota, Minneapolis 55455, USA.
Eiden
L E
LE
Cavert
W
W
Reinhart
T A
TA
Rausch
D M
DM
Murray
E A
EA
Weihe
E
E
Haase
A T
AT
D000818:Animals; D002490:Central Nervous System / Q000821:virology; D003072:Cognition Disorders; D003712:Dendrites / Q000473:pathology*; D018792:Encephalitis, Viral / Q000201:enzymology* / Q000473:pathology; D008253:Macaca mulatta; D009043:Motor Activity; D009474:Neurons; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D016097:Simian Acquired Immunodeficiency Syndrome / Q000201:enzymology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D014779:Virus Replication
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II