Role of porcine reproductive and respiratory syndrome virus nucleocapsid protein in induction of interleukin-10 and regulatory T-lymphocytes (Treg)

• DOI: 10.1099/vir.0.040287-0
• Publication Date: 2012-03-15T01:01:00Z
• Authors: Piya Wongyanin; Supranee Buranapr...; Dongwan Yoo; Roongroje Thanawo...; James A. Roth; Sanipa Suradhat
• Keywords: 0303 health sciences; Swine; Porcine Reproductive and Respiratory Syndrome; Dendritic Cells; Nucleocapsid Proteins; Lymphocyte Activation; T-Lymphocytes, Regulatory; Interleukin-10; Up-Regulation; 3. Good health; 03 medical and health sciences; Macrophages, Alveolar; Animals; Porcine respiratory and reproductive syndrome virus

Porcine reproductive and respiratory syndrome virus (PRRSV) infection induces interleukin (IL)-10 production and increased numbers of PRRSV-specific regulatory T-lymphocytes in infected pigs. In the present study, the roles of the nucleocapsid (N) protein in induction of IL-10 and CD4+CD25+Foxp3+lymphocytes (Treg) were investigated. Transfection of porcine monocyte-derived dendritic cells (MoDCs) and pulmonary alveolar macrophages (PAMs) with a plasmid encoding N protein resulted in significant upregulation of IL-10 gene expression in the gene-transfected cells. Structural conformation, but not nuclear localization, of the expressed N protein was indicated to be essential for the ability to induce IL-10. Furthermore, the presence of recombinant N proteins in cultured PBMCs increased the number of IL-10-producing lymphocytes. Strong induction of IL-10-producing cells and Tregwas observed when using N protein-pulsed MoDCs, suggesting an important role of MoDCs in induction of IL-10 and Tregby the N protein. Neutralization of IL-10 by addition of an anti-IL-10 antibody in the culture system resulted in marked reduction of PRRSV-induced Tregin the cultured PBMCs. Together, the data demonstrate the immunomodulatory properties of the PRRSV N protein and the linkage between IL-10 production and development of PRRSV-induced Treg. Our results reveal an immunomodulatory function of the PRRSV N protein that may contribute to the unique immunological outcome observed following PRRSV infection.