This study addressed an important question about the immunological interactions between PCV2 and PRRSV. Although PCV2 has been recognized as the major contributor to PCVAD, it is difficult to reproduce the disease with PCV2 alone. Typically infection by other viruses including PRRSV is required for clinical disease. However, the contribution each virus makes to the manifestation of clinical disease is unknown, but is presumed to be a result of immune modulation by the viruses. This research attempted to identify the contribution of each virus in enhancing disease. Understanding the effects of each virus on the immune system and how they interact is vital for vaccine development and for instituting other control measures. The objectives of this proposal were to determine how PCV2 infection enhances susceptibility to PRRSV; and to determine how PRRSV modulates the immune response to enhance PCV2-mediated clinical disease. Other investigators have shown that PCV2 infection results in dendritic cell (DC) maturation that produces IL-10 when infected with PRRSV. We have shown that PRRSV infection results in activation of regulatory T cells (Tregs) in acutely infected pigs. The results of these experiments show that PCV2 is more capable than PRRSV of activating regulatory T cells alone, and the Treg activation is enhanced by PRRSV and PCV-2 co-infection. Since Tregs are capable of non-specifically dampening the immune response to other pathogens as well, both PCV2 and PRRSV-mediated activation of Tregs will likely result in more severe disease when pigs are exposed to other pathogens. Additionally, the enhanced effect on Treg activation by PCV-2/PRRSV co-infection suggests that this mechanism may account for the manifestation of more severe PRRSV-related diseases in PCV-2 positive pigs. Further studies are needed to determine if pigs chronically infected with PCV-2 are more susceptible to PRRSV-mediated immunosuppression than pigs co-infected with PRRSV and PCV-2. However, it is clear from these studies that PCV-2 plays a big role in PRRSV-mediated immunosuppression, and both viruses should be considered when designing vaccines and vaccination strategies. For more information, contact Tanya LeRoith ([email protected]).