PMID- 24965453
OWN - NLM
STAT- MEDLINE
DCOM- 20150122
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 88
IP  - 18
DP  - 2014 Sep
TI  - Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine 
      reproductive and respiratory syndrome virus entry.
PG  - 10448-58
LID - 10.1128/JVI.01117-14 [doi]
AB  - As a consequence of their effects on ectodomain shedding, members of the A 
      disintegrin and metalloprotease (ADAM) family have been implicated in the control 
      of various cellular processes. Although ADAM family members are also involved in 
      cancer, inflammation, and other pathologies, it is unclear whether they affect 
      porcine reproductive and respiratory syndrome virus (PRRSV) infection. Here, we 
      demonstrate for the first time that inhibition of ADAM17 enhances PRRSV entry in 
      Marc-145 and porcine alveolar macrophages (PAMs). We also demonstrate that the 
      inhibition of ADAM17 upregulates membrane CD163 expression, a putative PRRSV 
      receptor that is exogenously expressed in BHK-21 and endogenously expressed in 
      Marc-145 and PAMs. Furthermore, overexpression of ADAM17 induced downregulation 
      of CD163 expression and a reduction in PRRSV infection, whereas ablation of 
      ADAM17 expression using specific small interfering RNA resulted in upregulation 
      of CD163 expression with a corresponding increase in PRRSV infection. These 
      ADAM17-mediated effects were confirmed with PRRSV nonpermissive BHK-21 cells 
      transfected with CD163 cDNA. Overall, these findings indicate that ADAM17 
      downregulates CD163 expression and hinders PRRSV entry. Hence, downregulation of 
      ADAM17 particular substrates may be an additional component of the anti-infection 
      defenses. IMPORTANCE: ADAM17 is one of the important membrane-associated 
      metalloproteases that mediate various cellular events, as well as inflammation, 
      cancer, and other pathologies. Here, we investigate for the first time the role 
      of the metalloprotease ADAM17 in PRRSV infection. By using inhibitor and genetic 
      modification methods, we demonstrate that ADAM17 negatively regulate PRRSV entry 
      by regulating its substrate(s). More specifically, ADAM 17 mediates the 
      downregulation of the PRRSV cellular receptor CD163. The reduction in CD163 
      expression represents another component of the anti-infection response initiated 
      by ADAM17.
CI  - Copyright (c) 2014, American Society for Microbiology. All Rights Reserved.
FAU - Guo, Longjun
AU  - Guo L
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Niu, Junwei
AU  - Niu J
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Yu, Haidong
AU  - Yu H
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Gu, Weihong
AU  - Gu W
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Li, Ren
AU  - Li R
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Luo, Xiaolei
AU  - Luo X
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Huang, Mingming
AU  - Huang M
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Tian, Zhijun
AU  - Tian Z
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Feng, Li
AU  - Feng L
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
FAU - Wang, Yue
AU  - Wang Y
AD  - State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research 
      Institute, Chinese Academy of Agricultural Sciences, Harbin, China 
      wangyue@hvri.ac.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140625
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD163 antigen)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Virus)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
SB  - IM
EIN - J Virol. 2016 May 12;90(11):5532. PMID: 27174637
MH  - ADAM Proteins/genetics/*metabolism
MH  - ADAM17 Protein
MH  - Animals
MH  - Antigens, CD/*genetics/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/*genetics/metabolism
MH  - Cell Line
MH  - Porcine Reproductive and Respiratory 
      Syndrome/enzymology/*genetics/metabolism/virology
MH  - Porcine respiratory and reproductive syndrome virus/*physiology
MH  - Receptors, Cell Surface/*genetics/metabolism
MH  - Receptors, Virus/genetics/metabolism
MH  - Swine
MH  - *Virus Internalization
PMC - PMC4178901
EDAT- 2014/06/27 06:00
MHDA- 2015/01/23 06:00
PMCR- 2015/03/01
CRDT- 2014/06/27 06:00
PHST- 2014/06/27 06:00 [entrez]
PHST- 2014/06/27 06:00 [pubmed]
PHST- 2015/01/23 06:00 [medline]
PHST- 2015/03/01 00:00 [pmc-release]
AID - JVI.01117-14 [pii]
AID - 01117-14 [pii]
AID - 10.1128/JVI.01117-14 [doi]
PST - ppublish
SO  - J Virol. 2014 Sep;88(18):10448-58. doi: 10.1128/JVI.01117-14. Epub 2014 Jun 25.