BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairments in cognition, behavior, and motor skills. The mechanism(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-gamma (IFNgamma), and interleukin 1 beta (IL-1 beta) 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, IFN gamma, and IL-1 beta 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.
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) can lead to severe impairments in cognition, behavior, and motor skills. The mechanism(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-gamma (IFNgamma), and interleukin 1 beta (IL-1 beta) 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, IFN gamma, and IL-1 beta 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.
Authors: H Kestler; T Kodama; D Ringler; M Marthas; N Pedersen; A Lackner; D Regier; P Sehgal; M Daniel; N King Journal: Science Date: 1990-06-01 Impact factor: 47.728
Authors: L M Grimaldi; G V Martino; D M Franciotta; R Brustia; A Castagna; R Pristerà; A Lazzarin Journal: Ann Neurol Date: 1991-01 Impact factor: 10.422
Authors: K Asano; C B Chee; B Gaston; C M Lilly; C Gerard; J M Drazen; J S Stamler Journal: Proc Natl Acad Sci U S A Date: 1994-10-11 Impact factor: 11.205
Authors: Gurudutt Pendyala; Elizabeth J Want; William Webb; Gary Siuzdak; Howard S Fox Journal: J Neuroimmune Pharmacol Date: 2006-10-10 Impact factor: 4.147
Authors: E M E Burudi; M Cecilia G Marcondes; Debbie D Watry; Michelle Zandonatti; Michael A Taffe; Howard S Fox Journal: J Virol Date: 2002-12 Impact factor: 5.103
Authors: Mary Jane Potash; Wei Chao; Galina Bentsman; Nicolae Paris; Manisha Saini; Jadwiga Nitkiewicz; Paula Belem; Leroy Sharer; Andrew I Brooks; David J Volsky Journal: Proc Natl Acad Sci U S A Date: 2005-02-23 Impact factor: 11.205