VP7 of Rhesus monkey rotavirus RRV contributes to diabetes acceleration in association with an elevated anti-rotavirus antibody response

- The ability of animal rotaviruses to accelerate type 1 diabetes in NOD8.3 mice was determined.
- Rotaviruses UK, SA11 and CRW-8 do not accelerate diabetes, in contrast to RRV.
- Diabetes is accelerated by reassortants containing RRV VP7 on a UK genetic background.
- Diabetes acceleration by these reassortants depends on a high serum anti-rotavirus antibody titer.
- Both VP7 and an elevated antibody response contribute to diabetes acceleration by RRV.

T cell-receptor transgenic NOD8.3 mice provide a model for spontaneous type 1 diabetes development. Infection of 5 week-old NOD8.3 mice with Rhesus monkey rotavirus (RRV) accelerates the onset of their diabetes. This acceleration requires virus replication and relates to the presence and level of serum anti-rotavirus antibodies, but the role of individual RRV genes is unknown. Here we assessed the importance for diabetes acceleration of the RRV genes encoding VP4 and VP7, by infecting NOD8.3 mice with parental and reassortant rotaviruses. Diabetes was accelerated by reassortant rotaviruses containing RRV VP7 on a UK rotavirus genetic background, but not by parental UK or a UK reassortant containing RRV VP4 without VP7. Diabetes acceleration by reassortant rotaviruses containing RRV VP7 depended on the development of a high serum anti-rotavirus antibody titer. This study shows that VP7, together with an elevated anti-rotavirus antibody response, contributes to the acceleration of diabetes onset by RRV.