Viral infections as potential triggers of type 1 diabetes.
During the last decades, the incidence of type 1 diabetes (T1D) has increased significantly, reaching percentages of 3% annually worldwide. This increase suggests that besides genetical factors environmental perturbations (including viral infections) are also involved in the pathogenesis of T1D. T1D has been associated with viral infections including enteroviruses, rubella, mumps, rotavirus, parvovirus and cytomegalovirus (CMV). Although correlations between clinical presentation with T1D and the occurrence of a viral infection that precedes the development of overt disease have been recognized, causalities between viruses and the diabetogenic process are still elusive and difficult to prove in humans. The use of experimental animal models is therefore indispensable, and indeed more insight in the mechanism by which viruses can modulate diabetogenesis has been provided by studies in rodent models for T1D such as the biobreeding (BB) rat, nonobese diabetic (NOD) mouse or specific transgenic mouse strains. Data from experimental animals as well as in vitro studies indicate that various viruses are clearly able to modulate the development of T1D via different mechanisms, including direct beta-cell lysis, bystander activation of autoreactive T cells, loss of regulatory T cells and molecular mimicry. Data obtained in rodents and in vitro systems have improved our insight in the possible role of viral infections in the pathogenesis of human T1D. Future studies will hopefully reveal which human viruses are causally involved in the induction of T1D and this knowledge may provide directions on how to deal with viral infections in diabetes-susceptible individuals in order to delay or even prevent the diabetogenic process.
van der Werf
Nienke
N
Department of Cell Biology, Immunology Section, University Medical Center Groningen, University of Groningen, The Netherlands.
Kroese
Frans G M
FG
Rozing
Jan
J
Hillebrands
Jan-Luuk
JL
D000818:Animals; D018188:Cardiovirus Infections / Q000150:complications; D003586:Cytomegalovirus Infections / Q000150:complications; D003921:Diabetes Mellitus, Experimental / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D004686:Encephalomyocarditis virus; D004769:Enterovirus Infections / Q000150:complications; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D009107:Mumps / Q000150:complications; D010322:Parvoviridae Infections / Q000150:complications; D051381:Rats; D011913:Rats, Inbred BB; D012400:Rotavirus Infections / Q000150:complications; D014777:Virus Diseases / Q000150:complications*