Encephalomyocarditis virus and diabetes mellitus: studies on virus mutants in susceptible and non-susceptible mice.

The so-called M-variant (especially subtype D) of encephalomyocarditis virus (EMCV) induces a diabetes-like syndrome in certain mouse strains which may serve as a model of insulin-dependent diabetes mellitus (IDDM) in man. The development and course of diabetes was influenced by a number of virus and host factors, among these being virus strain, virus dose, mouse strain, age, sex, and the host's immunological status. In a D-variant stock of EMCV, we found a virus plaque variant (PV 2) diabetogenic for DBA/2 mice, and at least one variant (PV 7) that did not affect carbohydrate metabolism. Although the diabetogenicity of PV 2 proved to be a genetically stable characteristic after further passages in vivo and in vitro, the incidence of diabetes varied somewhat (mean value 65% in 10-week-old DBA/2 mice infected with 10(5) p.f.u.). Both lower (10(1) or 10(3) p.f.u.) and higher (10(7) or 10(8) p.f.u.) virus doses led to a diminished incidence and severity of diabetes. In younger animals (5 weeks) transient hyperglycaemia often appeared, whereas in older animals (20 weeks) there was a higher rate of mortality. Histological examination of the islets of Langerhans in diabetes-susceptible (DBA/2) and resistant (C57BL/6) mice revealed that EMCV-induced hyperglycaemia appeared to develop in parallel to islet cell damage. Even in diabetic animals, some unaffected islets were regularly found. This study demonstrates that EMCV mutants may have completely different biological effects and produce diabetes only in special circumstances. Host factors play a significant role in the development of diabetes.