#07-103

Complete

Date Full Report Received

07/30/2009

Date Abstract Report Received

07/30/2009

Investigation

Institution:
Primary Investigator:

This study addressed an important question in the mechanism of persistence and immune suppression by PRRSV. PRRSV persistence currently is a major problem in the field. However, the mechanism by which the virus evades the immune system leading to persistent infection is not currently known. Additionally, the contribution of regulatory T cells in the pathogenesis of PRRS is not clear. The research outlined in this proposal allowed us to evaluate the role of the regulatory immune response in PRRSV pathogenesis. The hypothesis that PRRSV persistence and immune suppression occurs as a result of the ability of the virus to induce regulatory T cells was tested by two objectives. In the first objective, we aimed to determine if the number of regulatory T cells increased over the course of PRRS infection. In the second objected the aim was to determine if persistently infected pigs had higher numbers of Tregs than pigs that were able to clear the infection. To complete objective 1, we first inoculated pigs with PRRSV and assessed the ability of the virus to induce Tregs at 7 and 14 days post infection. By day 14, an increase in a subset of Tregs was detected in both the blood and lungs. For objective 2, we then inoculated a second group of pigs and followed them out to 42 days post infection to determine if the number of Tregs increased. No detectable increase in Tregs was found in the blood or lungs of pigs after 14 days post infection. These results suggest that Tregs are induced by PRRSV early in viral infection, and although they may not be significantly increased in persistently infected pigs, they likely play a role in the pathogenesis of PRRS by allowing the virus to evade protective immunity. Additionally, non-specifically dampening the immune response to other pathogens would result in secondary infections. Further studies to understand the role of regulatory T cells in PRRS pathogenesis is necessary to optimize the selection of vaccine adjuvants that will not only protect against PRRSV infection and persistence, but also minimize the immune-suppressive effects against other vaccines and pathogens. Knowing that PRRSV induces regulatory T cells is crucial in the design of new vaccines.