asialo-gm1-ganglioside and Enterovirus-Infections

The involvement of natural killer (NK) cells in the development of diabetes in the normally resistant 9-10 week old C57BL/6J male mice by the D variant of encephalomyocarditis virus (EMCV-D) was examined. Inoculation of purified EMCV-D induced maximum NK cell activity in splenic cell populations on day 4 post-inoculation as determined by lysis of YAC-1 target cells in a standard 51chromium release microcytotoxicity assay. Selective depletion of NK cells by the administration of rabbit anti-asialo GM1 sera prior to challenging the C57BL/6J mice with EMCV-D, resulted in diminished splenic NK cell activity, increased EMCV-D viral titers in the pancreas, spleen, heart and brain, and the induction of diabetes in 60-80% of the mice. The data suggest that NK cells play a role in host protection against the diabetogenic EMCV-D.

Topics: Animals; Diabetes Mellitus, Experimental; Encephalomyocarditis virus; Enterovirus Infections; G(M1) Ganglioside; Glucose Tolerance Test; Glycosphingolipids; Immune Sera; Killer Cells, Natural; Male; Mice; Mice, Inbred C57BL; Pancreas; Virus Replication

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.

Topics: Animals; Brain; Encephalomyocarditis virus; Enterovirus Infections; G(M1) Ganglioside; Glycosphingolipids; Interferons; Killer Cells, Natural; Lymphocytes; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Semliki forest virus; Togaviridae Infections; Tunicamycin; Virus Replication