Congenic B10.BR/SgSnJ H-2kTlaa mice were infected with a diabetogenic strain of coxsackievirus CB4 to correlate abnormalities of
sugar metabolism with virus replication in islets, 64,000-M(r) (
64K) islet autoantigen expression, 64K antibody development, and pancreas histopathology in early and late
infection. Plaque assay was used to measure virus replication, whereas immunoprecipitation of the mouse islet extracts with 64K antibody-positive and -negative human sera measured
autoantigen expression and antibody development. The infected mice exhibited
blood glucose values below that of the noninfected control animals at 72 h postinfection, this subnormal
blood glucose persisted at 6 wk postinfection and later. A baseline expression of the
autoantigen was detected in the noninfected mice; however, the infected animals did not overexpress the
protein at 72 h postinfection or develop 64K
antibodies after
infection. Limited virus replication was detected in the islets at 72 h postinfection but not later. Acinar
necrosis, but not islet loss due to mononuclear cell infiltration, was evident in the infected mice. The congenic mice did not develop
hyperglycemia and appear to be diabetes-resistant, their beta cells were largely preserved. This may be due to limited virus replication in their islets or their failure to overexpress the
autoantigen and develop 64K
antibodies following the
infection. Diabetes-susceptible mice, on the contrary, support active virus replication in their islets, overexpress the
autoantigen at 72 h postinfection, and develop 64K
antibodies and
hyperglycemia following such
infection (Gerling et al., 1988, 1991).