Mechanisms of cytokine-mediated inhibition of viral replication

In this report, the role of nitric oxide synthase (NOS) and IL-12 administr ation in inhibition of vesicular stomatitis virus (VSV) from infected neuro blastoma cells was examined. We previously have shown that cytokine treatme nt of cells results in the induction of NOS-1, and this is associated with a 2 log inhibition of VSV production. We performed these studies to examine the mechanism by which viral replication is suppressed. Neuroblastoma cell s (NB41A3) were treated with either IL-12 or medium and subsequently infect ed with VSV Viral protein and mRNA were isolated from these cells, and thei r levels were measured by Western or Northern blots, respectively. mRNA lev els were decreased modestly, but viral proteins were decreased substantiall y in cells pretreated with IL-12, suggesting that the inhibitory effect of NO is working at the translational level. Cytokine treatment of cells was n ot associated with oxidative stress. The viral proteins also were nitrosyla ted. These data suggest that the mechanism of NO inhibition of viral replic ation occurs through translational interference and posttranslational modif ications of viral components. (C) 1999 Academic Press.