Porcine reproductive and respiratory syndrome virus non-structural protein Nsp2TF down-regulates Swine Leukocyte Antigen class I (SLA class I) expression

Abstract

Abstract Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is arguably the most economically-important global swine pathogen. The virus typically induces sub-optimal immune responses especially a gradual increase of cellular immune-mediated (CMI) responses in the host. In this study, we demonstrated that PRRSV reduced SLA-I surface expression on porcine alveolar macrophages, monocyte-derived dendritic cells and a porcine kidney epithelial cell line, which may partly explain for the impaired CMI responses observed against PRRSV in pigs. To identify the PRRSV proteins responsible for SLA-I down-regulation, we screened all 22 PRRSV proteins by transient transfection assays. Our results indicated that Nsp1α, Nsp2TF and GP3 significantly down-regulated SLA-I surface expression of which Nsp2TF showed the greatest effect. To further validate whether Nsp2TF directly contributes to the PRRSV-induced SLA-I down-regulation, a panel of mutant viruses were generated with abolished Nsp2TF expression by disrupting −2 ribosomal frameshifting elements essential for the Nsp2TF protein synthesis as well as by introducing stop codons in TF domain of the protein. The infections with these mutant PRRSV strains fully restored the SLA-I surface expression in the infected cells. Additionally we demonstrated that the last 68 amino acids of TF domain are critical for this function. Our study for the first time uncovered an immune-modulatory function of PRRSV Nsp2TF in down-regulating SLA-I expression. Further studies are warranted to generate Nsp2TF-knockout vaccine strains and investigate their efficacies in inducing better CMI responses against the virus in pigs.