PMID- 22546080
OWN - NLM
STAT- MEDLINE
DCOM- 20130128
LR  - 20211021
IS  - 1743-422X (Electronic)
IS  - 1743-422X (Linking)
VI  - 9
DP  - 2012 Apr 30
TI  - Porcine reproductive and respiratory syndrome virus nonstructural protein 2 
      contributes to NF-kappaB activation.
PG  - 83
LID - 10.1186/1743-422X-9-83 [doi]
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) 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-kappaB in MARC-145 cells and alveolar 
      macrophages. The nucleocapsid (N) protein was identified as an NF-kappaB activator 
      among the structural proteins encoded by PRRSV; however, it remains unclear 
      whether the nonstructural proteins (Nsps) contribute to NF-kappaB activation. In this 
      study, we identified which Nsps can activate NF-kappaB 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-kappaB in MARC-145 
      and HeLa cells. Overexpression of Nsp2 induced IkappaBalpha degradation and nuclear 
      translocation of NF-kappaB. Furthermore, Nsp2 also induced NF-kappaB-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-kappaB activation. However, the 30-aa deletion was 
      demonstrated to not be associated with NF-kappaB activation. Further functional 
      domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential 
      for NF-kappaB 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.
FAU - Fang, Ying
AU  - Fang Y
AD  - 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.
FAU - Fang, Liurong
AU  - Fang L
FAU - Wang, Yang
AU  - Wang Y
FAU - Lei, Yingying
AU  - Lei Y
FAU - Luo, Rui
AU  - Luo R
FAU - Wang, Dang
AU  - Wang D
FAU - Chen, Huanchun
AU  - Chen H
FAU - Xiao, Shaobo
AU  - Xiao S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120430
PL  - England
TA  - Virol J
JT  - Virology journal
JID - 101231645
RN  - 0 (NF-kappa B)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 0 (Virulence Factors)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Epithelial Cells/immunology/virology
MH  - Humans
MH  - Macrophages, Alveolar/immunology/virology
MH  - NF-kappa B/*immunology
MH  - Porcine respiratory and reproductive syndrome virus/*immunology/*pathogenicity
MH  - Swine
MH  - Viral Nonstructural Proteins/*metabolism
MH  - Virulence Factors/*metabolism
PMC - PMC3443020
EDAT- 2012/05/02 06:00
MHDA- 2013/01/29 06:00
PMCR- 2012/04/30
CRDT- 2012/05/02 06:00
PHST- 2011/11/16 00:00 [received]
PHST- 2012/04/30 00:00 [accepted]
PHST- 2012/05/02 06:00 [entrez]
PHST- 2012/05/02 06:00 [pubmed]
PHST- 2013/01/29 06:00 [medline]
PHST- 2012/04/30 00:00 [pmc-release]
AID - 1743-422X-9-83 [pii]
AID - 10.1186/1743-422X-9-83 [doi]
PST - epublish
SO  - Virol J. 2012 Apr 30;9:83. doi: 10.1186/1743-422X-9-83.