Tunicamycin treatment inhibits the antiviral activity of interferon in mice

Earlier we reported that tunicamycin (TM) treatment of L cells in vitro significantly enhances the antiviral activity of interferon (IFN) against viruses (such as vesicular stomatitis, Sindbis, and herpes simplex) which bud from membranes. However, no such enhancement of the antiviral activity of IFN by TM was observed against encephalomyocarditis virus (EMCV) (nonbudding). We were interested to know whether TM would similarly enhance the antiviral activity of IFN and IFN inducers in vivo against Semliki Forest virus (SFV) and EMCV infections in mice. It was observed that TM alone (0.001 to 5.0 micrograms per mouse) did not protect mice against infections of SFV and EMCV; instead, TM-treated mice died with virus-specific paralytic symptoms earlier than untreated animals. The enhanced mortality in TM-treated and SFV- or EMCV-infected mice was associated with the concomitant increase in virus titer in brain tissue. IFN significantly protected mice against SFV and EMCV infections. The antiviral protection of mice by IFN against both the viruses was markedly inhibited by TM administration. IFN inducers (polyinosinic acid-polycytidylic acid, 6-MFA [a mixture of proteins, polysaccharides, and double-stranded DNA isolated from Aspergillus ochraceus ATCC 28706]) protected a significant number of mice against SFV infection. However, no such protection was observed in mice injected with a combination of TM and IFN inducer. These results indicate that TM treatment inhibits the antiviral action of IFN or IFN inducers in vivo.