title: Porcine reproductive and respiratory syndrome virus nonstructural protein 2 contributes to NF-κB activation.
abstract: BACKGROUND
  Nuclear factor-kappaB (NF-κB) is an inducible transcription factor that plays a key role in inflammation and immune responses, as well as in the regulation of cell proliferation and survival. Previous studies by our group and others have demonstrated that porcine reproductive and respiratory syndrome virus (PRRSV) infection could activate NF-κB in MARC-145 cells and alveolar macrophages. The nucleocapsid (N) protein was identified as an NF-κB activator among the structural proteins encoded by PRRSV; however, it remains unclear whether the nonstructural proteins (Nsps) contribute to NF-κB activation. In this study, we identified which Nsps can activate NF-κB and investigated the potential mechanism(s) by which they act.
  
  
  RESULTS
  By screening the individual Nsps of PRRSV strain WUH3, Nsp2 exhibited great potential to activate NF-κB in MARC-145 and HeLa cells. Overexpression of Nsp2 induced IκBα degradation and nuclear translocation of NF-κB. Furthermore, Nsp2 also induced NF-κB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, COX-2, and RANTES. Compared with the Nsp2 of the classical PRRSV strain, the Nsp2 of highly pathogenic PRRSV (HP-PRRSV) strains that possess a 30 amino acid (aa) deletion in Nsp2 displayed greater NF-κB activation. However, the 30-aa deletion was demonstrated to not be associated with NF-κB activation. Further functional domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential for NF-κB activation.
  
  
  CONCLUSIONS
  Taken together, these data indicate that PRRSV Nsp2 is a multifunctional protein participating in the modulation of host inflammatory response, which suggests an important role of Nsp2 in pathogenesis and disease outcomes.
authors.affiliation: Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, 1 Shizishan Street, Wuhan 430070, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fang
authors.forename: Liurong
authors.initials: L
authors.lastname: Fang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lei
authors.forename: Rui
authors.initials: R
authors.lastname: Luo
authors.forename: Dang
authors.initials: D
authors.lastname: Wang
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.forename: Shaobo
authors.initials: S
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology / Q000821:virology; D016328:NF-kappa B / Q000276:immunology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology* / Q000472:pathogenicity*; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors