Viruses and autoimmune diabetes in rats

Abstract

The role of viral infection in the pathogenesis of type 1 diabetes in humans remains an open question. Viruses are variously thought to be causative, preventive, or irrelevant. The rat models of the disease suggest that the role of viruses in the pathogenesis of autoimmunity can be multifaceted, with effects that are dependent on viral agent, host age, genetic background, and the immunological environment of the host at the time of infection. Among inbred strains with spontaneous onset of diabetes (BBDP, LEW.1AR1-iddm), the prevalence of disease generally increases with progressive removal of viruses from their environment. In contrast, in two rat strains with genetic susceptibility but little or no spontaneous diabetes in clean environments (BBDR, LEW.1WR1), infection with viruses from several families (parvovirus, enterovirus, poxvirus, herpesvirus) can trigger the disorder. The ability of viruses to do so is limited to juvenile animals, is dependent sensitively on the state of innate immunity before infections, and is strain dependent. Maternal immunization can prevent the onset of diabetes in infected offspring. The rat models of type 1 diabetes suggest that the role of infection in autoimmunity is complex but amenable to dissection.