K. Akarid et al., INHIBITORY EFFECT OF NITRIC-OXIDE ON THE REPLICATION OF A MURINE RETROVIRUS IN-VITRO AND IN-VIVO, Journal of virology, 69(11), 1995, pp. 7001-7005
Nitric oxide (NO) exerts microbicidal effects on a broad spectrum of p
athogens, including viruses, but its antiretrovirus properties have no
t yet been described. The purpose of this study was to determine wheth
er NO inhibits murine Friend leukemia virus (FV) replication in vitro
and to what extent NO may play a role in defenses against FV infection
in mice, Three NO-generating compounds were studied: 3-morpholino-syd
ononimine (SIN-1), sodium nitroprusside (SNP), and S-nitroso-N-acetylp
enicillamine (SNAP). The effects of these three compounds were compare
d with those of their controls (SIN-1C, potassium ferricyanide, and N-
acetylpenicillamine, respectively), which do not generate NO and with
that of sodium nitrite (NaNO2). SIN-1, SNP, and SNAP inhibited FV repl
ication in dunni cells in a concentration-dependent manner. In contras
t, no significant inhibitory effect was observed with the three contro
ls or NaNO2. Furthermore, the addition of superoxide dismutase did not
alter the inhibitory effect of SIN-1, which is also known to generate
superoxide anions, No dunni cell toxicity was observed in the range o
f concentrations tested. We also assessed the effect of NO produced by
activated macrophages on FV replication, Macrophages activated by gam
ma interferon and lipopolysaccharide inhibited FV replication in a con
centration-dependent manner. This inhibition was due in part to NO pro
duction, since it was reversed by N-G-monomethyl L-arginine, a competi
tive inhibitor of NO synthase, In vivo administration of N-G-nitro-L-a
rginine methyl ester, a competitive inhibitor of NO synthase, signific
antly increased the viral load in spleen cells of FV-infected mice, Th
ese results suggested that NO may play a role in defenses against the
murine Friend leukemia retrovirus.