Effect of coxsackievirus B4 infection in mice on expression of 64,000-Mr autoantigen and glucose sensitivity of islets before development of hyperglycemia.
Diabetogenic strains of Coxsackievirus B4 (CB4) produce a diabetes syndrome in susceptible mice that resembles insulin-dependent diabetes mellitus. To assess the possible role of autoimmunity, the expression of a 64,000-Mr islet antigen in SJL/J and CD1 mice infected with a diabetogenic strain of CB4 was monitored in early and late infection. Additionally, virus-induced abnormalities in glucose metabolism were correlated with several changes in purified islets to assess beta-cell physiology. Over 80% of the mice exhibited subnormal blood glucose at 72 h postinfection (p.i.) and were hyperglycemic at 6 and 8 wk p.i. Islet yield in infected mice decreased by 29-47% at 72 h and 6 wk p.i. compared to noninfected mice. Insulin release stimulated by 16.7 mM glucose increased greater than twofold at 72 h p.i. but declined at 6 wk well below the level of noninfected mice. Likewise, residual islet insulin content after release also increased at 72 h and then declined. Total protein synthesis in the islets decreased by 30% at 72 h and by 60% at 6 wk p.i. Although the synthesis of five proteins of heterogeneous molecular weights, including tubulin, was severely depressed in the infected islets at 72 h p.i. compared with control islets or islets at 6 wk p.i., synthesis of the 64,000-Mr component and another protein of 36,000 Mr increased by two- to threefold. It is possible that CB4 infection may initiate or enhance an autoimmune reaction by increased expression of the 64,000-Mr antigen.
Gerling
I
I
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Nejman
C
C
Chatterjee
N K
NK
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology; D029822:Enterovirus B, Human; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000209:etiology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008970:Molecular Weight
D001324:Autoantigens; D007328:Insulin; D005947:Glucose