Mutants were generated from diabetogenic D variant of encephalomycarditis(EMC-D) and nondiabetogenic EMC-B viruses by serial passage of virus in L929 cell at 10~100moi. In this study I isolated subvariants from EMC-D and EMC-B by plaque
purification and
studied their characteristics to understand diabetogenic factors.
Two highly diabetogenic subvariants(EMC-D2/4 and EMC-D1/6A) from EMC-D scarcely induced interferon, destructed mostβcells at pancreatic islets in vivo, had high efficiency of replication(10E9 TCID50/ml) and produced large plaque(6~8mm). Two
nondiabetogenic subvariants (EMC-D3/1 and EMC-D4/1B) from EMC-D scarcely induced interferon, fairly multiplied and then disappeared inβcell but didn't destructβcell in vivo, and had excellent efficiency of replication(3×10E9 TCID50/ml) but
produced
very small plaque(1~2mm). Subvariants(EMC-BS and EMC-BL) from EMC-B were nondiabetogenic, excellently induced interferon, fairly multiplied and then disappeared inβcell but didn't had fair efficiency of replication910E8 TCID50/ml) and produced
medium
sized plaque(3~6mm).
Genetic analysis of these subvariants showed that diabetogenic subvariants were different in one amino acid from nondiabetogenic subvariants. This difference inight affect viral attachment. but all EMC subvariants can attach to and multiply
inβcell. On
the basis of this and other studies, the nondiabetogenic viruses can directly destruct several kind of cells including βcell in vitro, but they can not destruct βcell in vivo because their replication may be blocked within 2 days after
infection
and
the infected cell can not tempt macrophage in spite of viral replication inβcell. I conclude that factors for the diabetogenicity of EMC virus may be rare induction of interferon, strong attachment capacity, high efficiency of replication and
large
plaque; and factors for the nondiabetogenicity may be capability of inducing some factors from host to block virial replication inβcell and not to provoke macrophage infiltration in pancreatic islets as well as weak attachment.
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