Background: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairnents in cognition, behavior, and motor skills. The mechanisms(s) by which HIV-1 induces CNS disease are not well understood. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) may contribute to HIV-1-induced neurologic disease. We sought to determine if these factors were present in the CNS of rhesus monkeys with simian immunodeficiency virus (SIV)-induced CNS disease. Materials and Methods: Total NO production in cerebral spinal fluid (CSF) from infected monkeys was determined by measuring nitrite (NO2-) and nitrate (NO3-) (stable NO degradation products) utilizing Greiss reagents. In situ hybridization revealed iNOS, interferon- γ (IFNγ), and interleukin 1β (IL-1β) mRNA in the brains of SIV-infected monkeys. Microglia were isolated from animals infected with SIV. Following stimulation with LPS, induction of iNOS mRNA in isolated microglia was analyzed by reverse transcriptase-polymerase chain reaction. Results: Serial CSF samples from an SIV-infected monkey reveal increased levels of NO2- /NO3-. In situ hybridization demonstrated iNOS, IFNγ, and IL-1β mRNAs in post-mortem brain tissue of SIV-infected monkeys. Furthermore, stimulated microglia from an SIV-infected monkey could produce iNOS mRNA. Conclusions: The presence of iNOS in the brain and NO2-/NO3- in the CSF indicates that NO is produced in the CNS of SIV-infected monkeys. The data suggest that iNOS and NO may be contributing to SIV-induced CNS disease.
|Original language||English (US)|
|Number of pages||11|
|State||Published - Dec 30 1996|
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology