Pc. Tucker et al., INHIBITION OF NITRIC-OXIDE SYNTHESIS INCREASES MORTALITY IN SINDBIS VIRUS ENCEPHALITIS, Journal of virology, 70(6), 1996, pp. 3972-3977
Sindbis virus (ST? is an alphavirus that causes acute encephalomyeliti
s 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 inf
ection with NSV, a neurovirulent strain of SV, were as follows: 81% (1
7 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 immun
odeficient scid/CB17 mice, Treatment with N omega-nitro-L-arginine met
hyl ester (L-NAME), a nitric oxide synthetase (NOS) inhibitor, increas
ed 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 a
nd BALB/cByJ mice had similar levels of inducible NOS mRNA in their br
ains, which were not affected by L-NAME or NSV infection, Brain NOS ac
tivity was similar in BALB/cJ and BALB/cByJ mice before and after infe
ction and was markedly inhibited by L-NAME. NSV replication in the bra
ins 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 infecti
on 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 vi
rus growth but rather may enhance survival of the infected neuron unti
l the immune response can control virus replication.