A RECOMBINANT VACCINIA VIRUS ENCODING INDUCIBLE NITRIC-OXIDE SYNTHASEIS ATTENUATED IN-VIVO

To investigate the role of nitric oxide during vacinia virus (VV) infe ction of mice, a recombinant VV encoding the inducible nitric oxide sy nthase (iNOS) gene (VV-HA-iNOS) was constructed. Following infection o f immunocompromised or immunocompetent mice, the virus was highly atte nuated compared with a control recombinant VV. Athymic and sublethally irradiated mice survived infection with 10(7) PFU of VV-HA-iNOS, a do se that resulted in uniform mortality in mice infected with the contro l recombinant VV. Attenuated virus growth was evident as early as 24 h following infection, suggesting that NO had direct antiviral activity . We have previously shown that treatment of mice with the inhibitor o f NO production N-G-methyl-L-arginine did not influence the course of VV infection in mice. The present study has indicated that NO can pote ntially exert an antiviral effect during murine VV infection. We propo se that during VV infection, nitric oxide production contributes to th e control of virus growth, but that in its absence, other antiviral me chanisms are sufficient to mediate fully effective virus clearance.