THE ANTIVIRAL ACTIVITY OF TUMOR-NECROSIS-FACTOR ON HERPES-SIMPLEX VIRUS TYPE-1 - ROLE FOR A BUTYLATED HYDROXYANISOLE SENSITIVE FACTOR

We have previously shown that specific antibodies (Mab 32/Ab 301) agai nst tumour necrosis factor (TNF) enhance its antiviral activity in vac cinia. virus-infected mice. In the present study, TNF alone was found to have antiviral activity against herpes simplex virus-1 (HSV-1). Ant ibody enhancement was found, both in vivo and in vitro, at lower TNF d oses. The magnitude of the TNF-induced antiviral response was dependen t upon the genetic background of the mouse. C57BL/6 mice were very sen sitive to the antiviral activity of TNF, which was inhibited by the fr ee radical scavenger butylated hydroxyanisole (BHA). TNF plus Mab 32 i nduced a significant antiviral effect in L929 cells which was associat ed with pronounced CPE. The CPE was largely reversed in the presence o f BHA, and furthermore, TNF antiviral activity was significantly rever sed in the presence of BHA. Specific inhibitors of nitric oxide synthe tase, lipoxygenase or cydo-oxygenase did not influence either the CPE or growth kinetics of HSV-1, suggesting that neither reactive nitrogen intermediates nor arachidonic acid metabolites were involved in the a ntiviral mechanism of TNF. This, together with observed increases in C u/Zn SOD levels in virus infected cells, suggests that reactive oxygen intermediates may have a role in the direct control of HSV-1 growth a nd that free radicals may play a part in the antiviral activity induce d by TNF.