title: The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I.
abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) is arguably the most economically-important global swine pathogen. Here we demonstrated that PRRSV down-regulates Swine Leukocyte Antigen class I (SLA-I) expression in porcine alveolar macrophages, PK15-CD163 cells and monocyte-derived dendritic cells. To identify the viral protein(s) involved in SLA-I down-regulation, we tested all 22 PRRSV structural and non-structural proteins and identified that Nsp1α and Nsp2TF, and GP3 significantly down-regulated SLA-I expression with Nsp2TF showing the greatest effect. We further generated a panel of mutant viruses in which the Nsp2TF protein synthesis was abolished, and found that the two mutants with disrupted -2 ribosomal frameshifting elements and additional stop codons in the TF domain were unable to down-regulate SLA-I expression. Additionally we demonstrated that the last 68 amino acids of TF domain in Nsp2TF are critical for this function. Collectively, the results indicate a novel function of Nsp2TF in negative modulation of SLA-I expression.
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, United States.
authors.forename: Qian M
authors.initials: QM
authors.lastname: Cao
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, United States.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, United States.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Ni
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, United States.
authors.forename: Dianjun
authors.initials: D
authors.lastname: Cao
authors.affiliation: Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, United States. Electronic address: xjmeng@vt.edu.
authors.forename: Xiang-Jin
authors.initials: XJ
authors.lastname: Meng
mesh_terms: D000818:Animals; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017361:Viral Nonstructural Proteins; C438668:swine leukocyte antigen
keywords: Down-regulation; Nsp1α; Nsp2TF; Porcine reproductive and respiratory syndrome virus (PRRSV); Swine Leukocyte Antigen class I (SLA-I)