PMID- 30158128
OWN - NLM
STAT- MEDLINE
DCOM- 20190722
LR  - 20190722
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 201
IP  - 8
DP  - 2018 Oct 15
TI  - Porcine Reproductive and Respiratory Syndrome Virus Nonstructural Protein 4 
      Cleaves Porcine DCP1a To Attenuate Its Antiviral Activity.
PG  - 2345-2353
LID - 10.4049/jimmunol.1701773 [doi]
AB  - As one of the most significant etiological agents in pigs, porcine reproductive 
      and respiratory syndrome virus (PRRSV) has adversely impacted the global swine 
      industry since it was discovered in the 1980s. The mRNA-decapping enzyme 1a 
      (DCP1a), a regulatory factor involved in removing the 5'-methylguanosine cap from 
      eukaryotic mRNA, has recently been identified as an IFN-stimulated gene. However, 
      the role of DCP1a in PRRSV infection is not well understood. In this study, 
      overexpression and knockdown of porcine DCP1a (pDCP1a) showed that pDCP1a 
      affected PRRSV infection. Interestingly, we found that PRRSV infection 
      significantly downregulated pDCP1a expression at the protein level by cleaving 
      pDCP1a. Furthermore, we demonstrated that PRRSV nonstructural protein 4 (nsp4), a 
      3C-like proteinase, is responsible for pDCP1a cleavage, and the cleaved site is 
      at glutamic acid 238 (E238) of pDCP1a. The mutant pDCP1a-E238A, which cannot be 
      cleaved by nsp4, showed higher anti-PRRSV activity, and the antiviral effects of 
      two cleavage products (pDCP1a(1-238) and pDCP1a(239-580)) were significantly 
      decreased compared with wild type pDCP1a. Unexpectedly, PRRSV infection or 
      overexpression of nsp4 did not cleave monkey DCP1a, and monkey DCP1a showed a 
      higher anti-PRRSV activity than pDCP1a. Taken together, this study reveals a new 
      strategy evolved by PRRSV to dampen the host defense, complementing the known 
      PRRSV-mediated immune evasion mechanisms.
CI  - Copyright (c) 2018 by The American Association of Immunologists, Inc.
FAU - Tao, Ran
AU  - Tao R
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
FAU - Fang, Liurong
AU  - Fang L
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
FAU - Bai, Dongcheng
AU  - Bai D
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
FAU - Ke, Wenting
AU  - Ke W
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
FAU - Zhou, Yanrong
AU  - Zhou Y
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
FAU - Wang, Dang
AU  - Wang D
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
FAU - Xiao, Shaobo
AU  - Xiao S
AUID- ORCID: 0000-0003-0023-9188
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan 430070, China; and 
      vet@mail.hzau.edu.cn.
AD  - Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The 
      Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180829
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antiviral Agents)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.15.- (dipeptidyl carboxypeptidase)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*metabolism
MH  - Cell Line
MH  - Down-Regulation
MH  - Endopeptidases/genetics/*metabolism
MH  - Glutamic Acid/genetics
MH  - Haplorhini
MH  - Host-Pathogen Interactions
MH  - Immune Evasion
MH  - Mutation/genetics
MH  - Porcine Reproductive and Respiratory Syndrome/*immunology
MH  - Porcine respiratory and reproductive syndrome virus/*physiology
MH  - Proteolysis
MH  - Signal Transduction
MH  - Species Specificity
MH  - Swine/*immunology/virology
MH  - Viral Nonstructural Proteins/*metabolism
EDAT- 2018/08/31 06:00
MHDA- 2019/07/23 06:00
CRDT- 2018/08/31 06:00
PHST- 2017/12/21 00:00 [received]
PHST- 2018/08/07 00:00 [accepted]
PHST- 2018/08/31 06:00 [pubmed]
PHST- 2019/07/23 06:00 [medline]
PHST- 2018/08/31 06:00 [entrez]
AID - jimmunol.1701773 [pii]
AID - 10.4049/jimmunol.1701773 [doi]
PST - ppublish
SO  - J Immunol. 2018 Oct 15;201(8):2345-2353. doi: 10.4049/jimmunol.1701773. Epub 2018 
      Aug 29.