PMID- 33181435
OWN - NLM
STAT- MEDLINE
DCOM- 20210715
LR  - 20210715
IS  - 1873-2542 (Electronic)
IS  - 0378-1135 (Linking)
VI  - 251
DP  - 2020 Dec
TI  - Wnt/beta-catenin signaling pathway inhibits porcine reproductive and respiratory 
      syndrome virus replication by enhancing the nuclear factor-kappaB-dependent innate 
      immune response.
PG  - 108904
LID - S0378-1135(20)31042-7 [pii]
LID - 10.1016/j.vetmic.2020.108904 [doi]
AB  - The Wnt/beta-catenin signaling pathway is an evolutionarily highly conserved 
      signaling pathway related to the replication of various viruses. However, the 
      interaction between the Wnt/beta-catenin pathway and porcine reproductive and 
      respiratory syndrome virus (PRRSV) is unknown. In the present study, we showed 
      that PRRSV-infected Marc-145 and PAM cells expressed high levels of c-myc and 
      cyclinD1 mRNA and accumulation of beta-catenin in the nucleus. PRRSV nonstructural 
      proteins (Nsps) 1alpha, 1beta, 3, 4, 7, 10, and 12, and proteins encoded by open reading 
      frames (ORFs) 2b, 3, and 5 induced the activation of the Wnt pathway according to 
      TOP/FOP luciferase reporter assay. But, Nsp5 inhibited the activation of the Wnt 
      pathway. Pre-treatment with Wnt3a inhibited PRRSV replication in Marc-145 cells 
      in a dose-dependent manner. Over-expression of beta-catenin also inhibited PRRSV 
      replication, while silencing of beta-catenin by small hairpin RNA increased its 
      replication in Marc-145 cells. Over-expression of beta-catenin increased interferon 
      regulatory factor (IRF)-3 expression and nuclear factor (NF)-kappaB phosphorylation, 
      NF-kappaB and interferon-stimulated response element promoter activities, and 
      interferon-beta, DExD/H-box helicase 58 (DDX58), interferon-induced protein with 
      tetratricopeptide repeats 1 (IFIT1), interleukin (IL)-1beta, tumor necrosis factor 
      (TNF)-alpha, and IL-8 mRNA expression. Conversely, silencing beta-catenin decreased 
      phosphorylated IRF-3 and NF-kappaB, NF-kappaB and IFIT1 promoter activities, and IFN-beta, 
      DDX58, IFIT1, IL-1beta, TNF-alpha, and IL-8 mRNA levels in Marc-145 cells. 
      Co-immunoprecipitation and immunofluorescence colocalization analyses confirmed 
      that beta-catenin interacted with NF-kappaB in Marc-145 cells. In conclusion, PRRSV 
      infection activates the Wnt/beta-catenin signaling pathway via Nsps 1alpha, 1beta, 3, 4, 7, 
      10, and 12, and proteins encoded by ORFs 2b, 3, and 5. The Wnt/beta-catenin pathway 
      then inhibits PRRSV replication by enhancing the NF-kappaB-dependent innate immune 
      response. These findings further our understanding of the role of the 
      Wnt/beta-catenin signaling pathway in regulating PRRSV replication and provide new 
      insights into virus-host interactions.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Wang, Jingyu
AU  - Wang J
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China; 
      Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 
      Province, 510642, People's Republic of China; National Engineering Research 
      Center for Breeding Swine Industry, South China Agricultural University, 
      Guangzhou, Guangdong Province, 510642, People's Republic of China.
FAU - Gong, Lang
AU  - Gong L
AD  - Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South 
      China Agricultural University, Guangzhou, Guangdong Province, 510642, People's 
      Republic of China.
FAU - Zhang, Weidong
AU  - Zhang W
AD  - Hospital of South China Agricultural University, Guangzhou, Guangdong Province, 
      510642, People's Republic of China.
FAU - Chen, Wanli
AU  - Chen W
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China.
FAU - Pan, Haoming
AU  - Pan H
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China.
FAU - Zeng, Yuchen
AU  - Zeng Y
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China.
FAU - Liang, Xingling
AU  - Liang X
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China.
FAU - Ma, Jun
AU  - Ma J
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China.
FAU - Zhang, Guihong
AU  - Zhang G
AD  - Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South 
      China Agricultural University, Guangzhou, Guangdong Province, 510642, People's 
      Republic of China; Guangdong Laboratory for Lingnan Modern Agriculture, 
      Guangzhou, Guangdong Province, 510642, People's Republic of China; National 
      Engineering Research Center for Breeding Swine Industry, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China. 
      Electronic address: guihongzh@scau.edu.cn.
FAU - Wang, Heng
AU  - Wang H
AD  - Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical 
      Animal Diseases, College of Veterinary Medicine, South China Agricultural 
      University, Guangzhou, Guangdong Province, 510642, People's Republic of China; 
      Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, Guangdong 
      Province, 510642, People's Republic of China; National Engineering Research 
      Center for Breeding Swine Industry, South China Agricultural University, 
      Guangzhou, Guangdong Province, 510642, People's Republic of China. Electronic 
      address: wangheng2009@scau.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20201023
PL  - Netherlands
TA  - Vet Microbiol
JT  - Veterinary microbiology
JID - 7705469
RN  - 0 (Viral Nonstructural Proteins)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - *Host-Pathogen Interactions
MH  - *Immunity, Innate
MH  - Macrophages, Alveolar/virology
MH  - Phosphorylation
MH  - Porcine respiratory and reproductive syndrome virus/*immunology/*physiology
MH  - *Signal Transduction
MH  - Swine
MH  - Viral Nonstructural Proteins/genetics
MH  - *Virus Replication
MH  - Wnt Signaling Pathway/*physiology
MH  - beta Catenin/metabolism
OTO - NOTNLM
OT  - IRF-3
OT  - Innate immune response
OT  - NF-kappaB
OT  - Porcine reproductive and respiratory syndrome virus
OT  - Wnt/beta-catenin signaling pathway
EDAT- 2020/11/13 06:00
MHDA- 2021/07/16 06:00
CRDT- 2020/11/12 20:14
PHST- 2020/08/13 00:00 [received]
PHST- 2020/10/18 00:00 [accepted]
PHST- 2020/11/13 06:00 [pubmed]
PHST- 2021/07/16 06:00 [medline]
PHST- 2020/11/12 20:14 [entrez]
AID - S0378-1135(20)31042-7 [pii]
AID - 10.1016/j.vetmic.2020.108904 [doi]
PST - ppublish
SO  - Vet Microbiol. 2020 Dec;251:108904. doi: 10.1016/j.vetmic.2020.108904. Epub 2020 
      Oct 23.