PMID- 28659471
OWN - NLM
STAT- MEDLINE
DCOM- 20170901
LR  - 20231213
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 91
IP  - 18
DP  - 2017 Sep 15
TI  - The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic 
      Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via 
      NF-kappaB and Sp1 Signaling Pathways.
LID - 10.1128/JVI.00986-17 [doi]
LID - e00986-17
AB  - Porcine reproductive and respiratory syndrome, caused by porcine reproductive and 
      respiratory syndrome virus (PRRSV), is a panzootic disease that is one of the 
      most economically costly diseases to the swine industry. A key aspect of PRRSV 
      virulence is that the virus suppresses the innate immune response and induces 
      persistent infection, although the underlying mechanisms are not well understood. 
      The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and 
      is associated with DC activation and immunosuppression of T cell proliferation 
      when expressed as soluble CD83 (sCD83). In this study, we show that PRRSV 
      infection strongly stimulates CD83 expression in porcine monocyte-derived DCs 
      (MoDCs) and that the nucleocapsid (N) protein and nonstructural protein 10 
      (nsp10) of PRRSV enhance CD83 promoter activity via the NF-kappaB and Sp1 signaling 
      pathways. R43A and K44A amino acid substitution mutants of the N protein suppress 
      the N protein-mediated increase of CD83 promoter activity. Similarly, P192-5A and 
      G214-3A mutants of nsp10 (with 5 and 3 alanine substitutions beginning at 
      residues P192 and G214, respectively) abolish the nsp10-mediated induction of the 
      CD83 promoter. Using reverse genetics, four mutant viruses (rR43A, rK44A, 
      rP192-5A, and rG214-3A) and four revertants [rR43A(R), rK44A(R), rP192-5A(R), and 
      rG214-3A(R)] were generated. Decreased induction of CD83 in MoDCs was observed 
      after infection by mutants rR43A, rK44A, rP192-5A, and rG214-3A, in contrast to 
      the results obtained using rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R). 
      These findings suggest that PRRSV N and nsp10 play important roles in modulating 
      CD83 signaling and shed light on the mechanism by which PRRSV modulates host 
      immunity.IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) 
      is one of the most economically costly pathogens affecting the swine industry. It 
      is unclear how PRRSV inhibits the host's immune response and induces persistent 
      infection. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin 
      superfamily and has previously been associated with DC activation and 
      immunosuppression of T cell proliferation and differentiation when expressed as 
      soluble CD83 (sCD83). In this study, we found that PRRSV infection induces sCD83 
      expression in porcine MoDCs via the NF-kappaB and Sp1 signaling pathways. The viral 
      nucleocapsid protein, nonstructural protein 1 (nsp1), and nsp10 were shown to 
      enhance CD83 promoter activity. Amino acids R43 and K44 of the N protein, as well 
      as residues 192 to 196 (P192-5) and 214 to 216 (G214-3) of nsp10, play important 
      roles in CD83 promoter activation. These findings provide new insights into the 
      molecular mechanism of immune suppression by PRRSV.
CI  - Copyright (c) 2017 American Society for Microbiology.
FAU - Chen, Xi
AU  - Chen X
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Zhang, Qiaoya
AU  - Zhang Q
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Bai, Juan
AU  - Bai J
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Zhao, Yongxiang
AU  - Zhao Y
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Wang, Xianwei
AU  - Wang X
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Wang, Haiyan
AU  - Wang H
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China.
FAU - Jiang, Ping
AU  - Jiang P
AD  - Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of 
      Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, 
      Nanjing, China jiangp@njau.edu.cn.
AD  - Jiangsu Co-Innovation Center for Prevention and Control of Important Animal 
      Infectious Diseases and Zoonoses, Yangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170824
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nucleocapsid Proteins)
RN  - 0 (Viral Nonstructural Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Sp1 kinase)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*biosynthesis
MH  - DNA Mutational Analysis
MH  - Dendritic Cells/immunology
MH  - Host-Pathogen Interactions
MH  - Immune Tolerance
MH  - Immunoglobulins/*biosynthesis
MH  - Membrane Glycoproteins/*biosynthesis
MH  - NF-kappa B/*metabolism
MH  - Nucleocapsid Proteins/genetics/*metabolism
MH  - Porcine respiratory and reproductive syndrome virus/*immunology
MH  - Protein Kinases/*metabolism
MH  - *Signal Transduction
MH  - Swine
MH  - T-Lymphocytes/immunology
MH  - Up-Regulation
MH  - Viral Nonstructural Proteins/genetics/*metabolism
MH  - CD83 Antigen
PMC - PMC5571251
OTO - NOTNLM
OT  - CD83
OT  - NF-kappaB
OT  - PRRSV
OT  - Sp1
OT  - nonstructural protein 10
OT  - nucleocapsid
EDAT- 2017/07/01 06:00
MHDA- 2017/09/02 06:00
PMCR- 2018/02/24
CRDT- 2017/06/30 06:00
PHST- 2017/06/14 00:00 [received]
PHST- 2017/06/14 00:00 [accepted]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2017/09/02 06:00 [medline]
PHST- 2017/06/30 06:00 [entrez]
PHST- 2018/02/24 00:00 [pmc-release]
AID - JVI.00986-17 [pii]
AID - 00986-17 [pii]
AID - 10.1128/JVI.00986-17 [doi]
PST - epublish
SO  - J Virol. 2017 Aug 24;91(18):e00986-17. doi: 10.1128/JVI.00986-17. Print 2017 Sep 
      15.