Characterization of Insulin-Dependent Diabetes Mellitus Induced by a New Variant (DK-27) of Encephalomyocarditis Virus in DBA/2 Mice.

Abstract

A murine diabetes mellitus induced with a new diabetogenic variant (DK-27) which we isolated from the M variant of the encephalomyocarditis (EMC) virus was characterized. Male DBA/2 mice (9.5 weeks old) were infected with various infectious doses of DK-27 intraperitoneally. Blood glucose and insulin levels were examined in association with the viral replication. Pancreatic pathology and hormone contents and stable hemoglobin A1c (St-A1c) levels were also examined on the final day of observation (35 days of post-infection). In infected mice, blood glucose levels rapidly elevated at 72 hr, slightly decreased between 7 and 10 days and finally became sustained hyperglycemia. On the other hand, blood insulin levels elevated at 48 hr, promptly decreased, and subsequently became sustained hypoinsulinemia. Viral replication in pancreases reached the highest titers at 48 hr and rapidly disappeared with all infectious doses used. Pancreatic insulin contents in infected mice were not detectable, and glucagon contents were not affected. In pathological examination, atrophy of islets and marked diminution of B-cells were observed, and A-cells occupied the major part of an infected islet. St-A1c levels reflected lasting hyperglycemia. These findings show that DK-27 causes insulin-dependent diabetes mellitus by the specific and direct destruction of pancreatic B-cells in susceptible mice. Such a diabetic model mouse will be useful for therapeutic studies.

The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon.

“…NS5A-expressing cells and the control were treated with murine IFN-α\β (Hotta et al, 1984) (kindly provided by M. Kohase, National Institute of Infectious Diseases, Tokyo) or mock-treated for 18 h and challenged with encephalomyocarditis virus (EMCV) [strain DK-27 (Dan et al, 1995) ; kindly provided by Y. Seto, Keio University, Tokyo], vesicular stomatitis virus (VSV, New Jersey strain) or Japanese encephalitis virus (JEV, Nakayama strain). Culture fluids were taken every day after infection and virus titres were measured by plaque assay on either L929 (EMCV and VSV) or Vero cells (JEV).…”

Hepatitis C virus NS5A protein interacts with 2′,5′-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner

“…Cells were seeded in six-well tissue culture plates at a density of 2610 5 cells per well and cultivated for 24 h. The cells were treated with recombinant mouse IFN-aA (PBL Biomedical Laboratory) or human IFN-a2a (Roche) at concentrations of 5 and 25 U ml 21 or left untreated for another 24 h, then inoculated with 50-60 p.f.u. EMCV (strain DK-27) per well (Dan et al, 1995;Song et al, 1999). After 1 h with intermittent rocking, fresh medium containing 1 % methylcellulose was added to each well of the plates.…”