Pseudorabies virus-induced expression of nitric oxide synthase isoforms.
In addition to its role as a neurotransmitter, studies have postulated both neuroprotective and neurotoxic roles for nitric oxide (NO) generated in response to infections with neurotropic viruses. This study examined the expression of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) isoforms of NOS induced by neuronal infection with virulent and attenuated strains of pseudorabies virus (PRV). Caudal brainstem neurons infected by peripheral inoculation of the viscera served as the model system. Neuronal infection induced the expression of nNOS and iNOS, but the timing and the apparent magnitude of NOS expression varied according to the virulence of the infecting strain of virus. Expression of nNOS was observed in infected neurons that did not express this enzyme in control animals, and the onset of expression was earlier in animals infected with virulent PRV. Expression of iNOS was largely restricted to monocytes and macrophages that invaded the brain in response to PRV infection. These iNOS-expressing cells were observed earlier in animals infected with the virulent virus, and were differentially concentrated in areas exhibiting virus-induced neuropathology. Collectively, these data suggest functionally diverse roles for NO in the brain response to PRV neuronal infection.
Serrano
Faridis
F
Department of Neuroscience, University of Pittsburgh, 446 Crawford Hall, 15260, Pittsburgh, PA, USA.
Enquist
Lynn W
LW
Card
J Patrick
JP
D000818:Animals; D005822:Genetic Vectors / Q000235:genetics*; D011558:Herpesvirus 1, Suid / Q000235:genetics*; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000201:enzymology; D008297:Male; D009000:Monocytes / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D011557:Pseudorabies / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014779:Virus Replication / Q000502:physiology
D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat