Lack of nitric oxide synthase type 2 (NOS2) results in reduced neuronal apoptosis and mortality following mouse hepatitis virus infection of the central nervous system.
The role of nitric oxide synthase type-2 (NOS2)-derived nitric oxide (NO) in the pathogenesis of mouse hepatitis virus (MHV)-induced central nervous system disease was examined. Infection of NOS2 knockout ((-/-)) and NOS2(+/+) mice with MHV resulted in similar kinetics of viral clearance from the brain and comparable levels of demyelination. MHV-infected NOS2(-/-) mice displayed a marked decrease in mortality as compared to infected NOS2(+/+) mice that correlated with a significant decrease (P < or = 0.001) in the number of apoptotic cells (determined by TUNEL staining) present in the brain. Confocal microscopy revealed that the majority of cells (>70%) undergoing apoptosis were neurons. These studies indicate that NOS2-generated NO contributes to apoptosis of neurons but not demyelination following MHV infection.
Chen
Benjamin P
BP
Department of Molecular Biology and Biochemistry, University of California-Irvine, Irvine, California, USA.
Lane
Thomas E
TE
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000201:enzymology / Q000473:pathology / Q000821:virology; D018352:Coronavirus Infections / Q000201:enzymology* / Q000473:pathology; D003711:Demyelinating Diseases / Q000201:enzymology / Q000473:pathology / Q000821:virology; D018792:Encephalitis, Viral / Q000201:enzymology / Q000473:pathology; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus; D009474:Neurons / Q000473:pathology / Q000821:virology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse