Infection with viruses from several families triggers autoimmune diabetes in LEW*1WR1 rats: prevention of diabetes by maternal immunization.
OBJECTIVE
The contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. Using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes.


METHODS
About 2% of LEW*1WR1 rats develop spontaneous autoimmune diabetes, but disease penetrance is much higher if weanling rats are exposed to environmental perturbants including Kilham rat virus (KRV). We compared KRV with other viruses for diabetogenic activity.


RESULTS
Both KRV and rat cytomegalovirus (RCMV) induced diabetes in up to 60% of LEW*1WR1 rats, whereas H-1, vaccinia, and Coxsackie B4 viruses did not. Simultaneous inoculation of KRV and RCMV induced diabetes in 100% of animals. Pretreatment of rats with an activator of innate immunity increased the diabetogenicity of KRV but not RCMV and was associated with a moderate rate of diabetes after Coxsackie B4 and vaccinia virus infection. Inoculation of LEW*1WR1 dams with both KRV and RCMV prior to pregnancy protected weanling progeny from virus-induced diabetes in a virus-specific manner.


CONCLUSIONS
Exposure to viruses can affect the penetrance of autoimmune diabetes in genetically susceptible animals. The diabetogenicity of infection is virus specific and is modified by immunomodulation prior to inoculation. Maternal immunization protects weanlings from virus-induced diabetes, suggesting that modification of immune responses to infection could provide a means of preventing islet autoimmunity.
BioMedical Research Models, Worcester, Massachusetts, USA.
Rebecca S
RS
Tirabassi
Dennis L
DL
Guberski
Elizabeth P
EP
Blankenhorn
Jean H
JH
Leif
Bruce A
BA
Woda
Zhijun
Z
Liu
Donald
D
Winans
Dale L
DL
Greiner
John P
JP
Mordes
D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D029822:Enterovirus B, Human / Q000276:immunology; D004769:Enterovirus Infections / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D023421:Models, Animal; D011070:Poly I-C / Q000276:immunology; D011247:Pregnancy; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014616:Vaccinia virus / Q000276:immunology; D014777:Virus Diseases / Q000150:complications* / Q000276:immunology*
D011070:Poly I-C