PMID- 32401783
OWN - NLM
STAT- MEDLINE
DCOM- 20200721
LR  - 20200721
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 16
IP  - 5
DP  - 2020 May
TI  - TREM2 suppresses the proinflammatory response to facilitate PRRSV infection via 
      PI3K/NF-kappaB signaling.
PG  - e1008543
LID - 10.1371/journal.ppat.1008543 [doi]
LID - e1008543
AB  - Triggering receptor expressed on myeloid cells 2 (TREM2) serves as an 
      anti-inflammatory receptor, negatively regulating the innate immune response. 
      TREM2 is mainly expressed on dendritic cells and macrophages, the target cells of 
      porcine reproductive and respiratory syndrome virus (PRRSV). Thus, we 
      investigated the potential role of TREM2 in PRRSV infection in porcine alveolar 
      macrophages (PAMs). We found that there was an increased expression of TREM2 upon 
      PRRSV infection in vitro. TREM2 silencing restrained the replication of PRRSV, 
      whereas TREM2 overexpression facilitated viral replication. The cytoplasmic tail 
      domain of TREM2 interacted with PRRSV Nsp2 to promote infection. TREM2 
      downregulation led to early activation of PI3K/NF-kappaB signaling, thus reinforcing 
      the expression of proinflammatory cytokines and type I interferons. Due to the 
      enhanced cytokine expression, a disintegrin and metalloproteinase 17 was 
      activated to promote the cleavage of membrane CD163, which resulted in 
      suppression of infection. Furthermore, exogenous soluble TREM2 (sTREM2)-mediated 
      inhibition of PRRSV attachment might be attributed to its competitive binding to 
      viral envelope proteins. In pigs, following PRRSV challenge in vivo, the 
      expression of TREM2 in lungs and lymph nodes as well as the production of sTREM2 
      were significantly increased. These novel findings indicate that TREM2 plays a 
      role in regulating PRRSV replication via the inflammatory response. Therefore, 
      our work describes a novel antiviral mechanism against PRRSV infection and 
      suggests that targeting TREM2 could be a new approach in the control of the PRRSV 
      infection.
FAU - Zhu, Zhenbang
AU  - Zhu Z
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Zhang, Xiaoxiao
AU  - Zhang X
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Dong, Wenjuan
AU  - Dong W
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Wang, Xiaoying
AU  - Wang X
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - He, Sheng
AU  - He S
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Wang, Xun
AU  - Wang X
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Wei, Ruiping
AU  - Wei R
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Chen, Yaosheng
AU  - Chen Y
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Liu, Xiaohong
AU  - Liu X
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
FAU - Guo, Chunhe
AU  - Guo C
AUID- ORCID: 0000-0002-7859-1985
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen 
      University, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, PR 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200513
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
SB  - IM
MH  - Animals
MH  - Inflammation/immunology/pathology/virology
MH  - Membrane Glycoproteins/*immunology
MH  - NF-kappa B/*immunology
MH  - Phosphatidylinositol 3-Kinases/*immunology
MH  - Porcine Reproductive and Respiratory Syndrome/*immunology/pathology
MH  - Porcine respiratory and reproductive syndrome virus/*immunology
MH  - Signal Transduction/*immunology
MH  - Swine
PMC - PMC7250469
COIS- The authors have declared that no competing interests exist.
EDAT- 2020/05/14 06:00
MHDA- 2020/07/22 06:00
PMCR- 2020/05/13
CRDT- 2020/05/14 06:00
PHST- 2019/12/06 00:00 [received]
PHST- 2020/04/14 00:00 [accepted]
PHST- 2020/05/26 00:00 [revised]
PHST- 2020/05/14 06:00 [pubmed]
PHST- 2020/07/22 06:00 [medline]
PHST- 2020/05/14 06:00 [entrez]
PHST- 2020/05/13 00:00 [pmc-release]
AID - PPATHOGENS-D-19-02179 [pii]
AID - 10.1371/journal.ppat.1008543 [doi]
PST - epublish
SO  - PLoS Pathog. 2020 May 13;16(5):e1008543. doi: 10.1371/journal.ppat.1008543. 
      eCollection 2020 May.