A genetically determined host factor controlling susceptibility to encephalomyocarditis virus-induced diabetes in mice.
Levels of insulin mRNA in pancreata from SJL/J male mice susceptible to encephalomyocarditis (EMC)-D virus-induced diabetes started to decrease rapidly 24 h after injection with EMC-D virus and only a trace remained 72 h after injection. In contrast, insulin mRNA in pancreata from C57BL/6J male mice resistant to EMC-D virus-induced diabetes did not show any significant changes 0 to 96 h after injection. EMC-D viral RNA in pancreata from SJL/J mice started to increase rapidly 24 h after injection, reached its peak at 48 h and then decreased gradually. In contrast, EMC-D viral RNA in pancreata from C57BL/6J mice was undetectable except for the 24 and 48 h points after injection. EMC-D virus could bind readily to freshly isolated beta cells from SJL/J mice but scarcely bound to beta cells from C57BL/6J mice. In contrast, there was no significant difference between SJL/J and C57BL/6J mice in binding of EMC-D virus to their cultured beta cells. The rate of EMC-D viral attachment to beta cells from C57BL/6J mice increased significantly during the first 24 h culture period and reached the same rate of attachment as that seen for beta cells from SJL/J mice. This suggests that viral receptors on the beta cells derived from strains of mice resistant to EMC virus-induced diabetes are not expressed in vivo, but are expressed during cell culture, rendering the beta cells susceptible to EMC viral infection. On the basis of our previous and present observations, we conclude that a genetic factor controlling susceptibility to EMC-D virus-induced diabetes may operate by modulating the expression of viral receptors on the beta cells.
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Alberta, Canada.
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Kang
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Yoon
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000235:genetics* / Q000382:microbiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics* / Q000382:microbiology; D004686:Encephalomyocarditis virus / Q000254:growth & development / Q000472:pathogenicity* / Q000648:ultrastructure; D004769:Enterovirus Infections / Q000150:complications*; D020022:Genetic Predisposition to Disease; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
D007328:Insulin; D012333:RNA, Messenger; D011991:Receptors, Virus