Inhibition of nitric oxide synthesis increases mortality in sindbis virus encephalitis

Pamela C. Tucker, Diane Griffin, Stephen Choi, Nam Bui, Steven Wesselingh

Research output: Contribution to journalArticle

Abstract

Sindbis virus (SV) is an alphavirus that causes acute encephalomyelitis in mice. The outcome is determined by the strain of virus and by the age and genetic background of the host. The mortality rates after infection with NSV, a neurovirulent strain of SV, were as follows: 81% (17 of 21) in BALB/cJ mice; 20% (4 of 20) in BALB/cByJ mice (P <0.001); 100% in A/J, C57BL/6J, SJL, and DBA mice; and 79% (11 of 14) in immunodeficient scid/CB17 mice. Treatment with Nω-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthetase (NOS) inhibitor, increased mortality to 100% (P <0.05) in NSV- infected BALB/cJ mice, to 95% (P <0.001) in BALB/cByJ mice, and to 100% in scid/CB17 mice. BALB/cJ and BALB/cByJ mice had similar levels of inducible NOS mRNA in their brains, which were not affected by L-NAME or NSV infection. Brain NOS activity was similar in BALB/cJ and BALB/cByJ mice before and after infection and was markedly inhibited by L-NAME. NSV replication in the brains of BALB/cJ mice, BALB/cByJ mice, and mice treated with L-NAME was similar. Treatment of N18 neuroblastoma cells with NO donors S-nitroso-N- acetylpenicillamine or sodium nitroprusside in vitro before infection increased cell viability at 42 to 48 h compared with untreated NSV-infected N18 cells with little effect on virus replication. These data suggest that NO protects mice from fatal encephalitis by a mechanism that does not directly involve the immune response or inhibition of virus growth but rather may enhance survival of the infected neuron until the immune response can control virus replication.

Original languageEnglish (US)
Pages (from-to)3972-3977
Number of pages6
JournalJournal of Virology
Volume70
Issue number6
StatePublished - 1996

Fingerprint

Sindbis virus
Sindbis Virus
Encephalitis
encephalitis
nitric oxide
Nitric Oxide
synthesis
Mortality
mice
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Virus Replication
Infection
virus replication
nitric oxide synthase
brain
infection
Brain
S-Nitroso-N-Acetylpenicillamine
Alphavirus

ASJC Scopus subject areas

  • Immunology

Cite this

Tucker, P. C., Griffin, D., Choi, S., Bui, N., & Wesselingh, S. (1996). Inhibition of nitric oxide synthesis increases mortality in sindbis virus encephalitis. Journal of Virology, 70(6), 3972-3977.

Inhibition of nitric oxide synthesis increases mortality in sindbis virus encephalitis. / Tucker, Pamela C.; Griffin, Diane; Choi, Stephen; Bui, Nam; Wesselingh, Steven.

In: Journal of Virology, Vol. 70, No. 6, 1996, p. 3972-3977.

Research output: Contribution to journalArticle

Tucker, PC, Griffin, D, Choi, S, Bui, N & Wesselingh, S 1996, 'Inhibition of nitric oxide synthesis increases mortality in sindbis virus encephalitis', Journal of Virology, vol. 70, no. 6, pp. 3972-3977.
Tucker, Pamela C. ; Griffin, Diane ; Choi, Stephen ; Bui, Nam ; Wesselingh, Steven. / Inhibition of nitric oxide synthesis increases mortality in sindbis virus encephalitis. In: Journal of Virology. 1996 ; Vol. 70, No. 6. pp. 3972-3977.
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