Virus-induced diabetes mellitus. X. Attachment of encephalomyocarditis virus and permissiveness of cultured pancreatic β cells to infection

Abstract

Monolayers of pancreatic p-cells from strains of mice susceptible @IL/J) and resistant (C57BL/&l) to the development of virus-induced diabetes mellitus were inoculated with the M variant of encephalomyocarditis (EMC) virus. Immunofluorescence showed that viral antigens appeared in up to 10 times more /3 cells from susceptible &IL/J mice than from resistant C57BLKJ mice. Infectious center assays revealed that lo-30 times more &IL/J /I cells contained infectious virus than C57BLFJ p cells. Viral attachment experiments showed no difference in the binding of EMC virus when embryonic fibroblasts, pancreatic fibroblasts, and kidney cells from SJLlJ and C57BL/&J mice were compared. However, at least twice as much virus attached to the pancreatic /3 cells from susceptible than from resistant strains of mice. Our data suggest that genetically determined differences in viral receptors on the surface of fi cells may be one of the factors controlling susceptibility to EMC-induced diabetes mellitus. 606

Virus and Insulin-Dependent Diabetes Mellitus

“…The inability of the virus to cause diabetes in nonsusceptible mice could result from the lack of viral receptors on the beta cells. Evidence to support this hypothesis was reported by Chairez et al (1978). Nearly 10 times more virus was found in susceptible beta cells than in nonsusceptible cells.…”

A genetically determined host factor controlling susceptibility to encephalomyocarditis virus-induced diabetes in mice

“…Earlier studies with the M variant of encephalomyocarditis (EMC-M) virus, which contains a mixture of diabetogenic EMC-D and non-diabetogenic EMC-B, suggested that the genetic factors controlling susceptibility to EMC virus-induced diabetes may operate at the level of insulin-producing beta cells (Chairez et al, 1978;Onodera et al, 1978;Yoon & Notkins, 1976). After infection in vivo with EMC-M virus, beta cells from susceptible mice showed significantly higher viral titres than beta cells from resistant mice Yoon & Notkins, 1976); however, there was no significant difference in EMC-M viral susceptibility in 9 day cultured beta cells between the susceptible strain (CD-1) and the resistant strain (C57BL/6J) (Wilson et al, 1980).…”

Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4.

“…Moreover, recent data suggest that a single locus may control susceptibility (28). Based on these observations, it has been postulated (but not proven) that the gene product controlling susceptibility might be a receptor for the virus on the surface of beta ceils (29). If this turns out to be the case, then it would not be unreasonable to suspect that host-determined differences in the induction of diabetes by Coxsackie virus B4 also might be related to viral receptors on the surface of beta cells.…”

“…The only exception, thus far, appears to be DBA/1J and DBA/2J mice which developed diabetes when exposed to EMC virus (26), but did not develop diabetes when exposed to Coxsackie virus B4. In the case of EMC virus, it is known that susceptibility to diabetes is inherited as an autosomal recessive trait (24,28), and that beta cells from strains of mice that develop diabetes are more susceptible to EMC infection than beta cells from strains of mice that do not develop diabetes (18,27,29). Moreover, recent data suggest that a single locus may control susceptibility (28).…”