Tunicamycin enhances virus replication and inhibits antiviral activity of interferon in mice: correlation with natural killer cells.

Abstract

Earlier we reported that tunicamycin (TM) treatment enhances Semliki Forest virus (SFV) and encephalomyocarditis virus (EMCV) replication in Swiss mice. Interferon (IFN) mediated antiviral protection was also inhibited in mice treated with TM. The in vitro natural killer (NK) cell reactivity of mice was significantly decreased after in vivo administration of TM; however, TM treatment did not affect the response of the same cells to mitogens. TM also inhibited the boosting of NK reactivity by IFN in vivo. In this paper, we have shown that depletion of NK cells by asialo-GM1 antiserum enhances SFV/EMCV replication in mice. Both TM and anti-asialo GM1 treatment significantly inhibited the large granular lymphocyte (LGL) populations in the spleen. Similar to Swiss mice, the in vitro NK cell activity of athymic nude mice was significantly decreased after in vivo administration of TM and TM also inhibited the boosting effect on NK cells reactivity induced by IFN in vivo. TM treatment of nude mice also enhanced the SFV/EMCV in brains of infected mice and also inhibited the antiviral activity of IFN in nude mice. These results suggest that NK cells may be involved in SFV/EMCV infection and in antiviral protection afforded by IFN.