PMID- 27066702
OWN - NLM
STAT- MEDLINE
DCOM- 20161013
LR  - 20171116
IS  - 1873-2542 (Electronic)
IS  - 0378-1135 (Linking)
VI  - 187
DP  - 2016 May 1
TI  - Downregulation of protein kinase PKR activation by porcine reproductive and 
      respiratory syndrome virus at its early stage infection.
PG  - 1-7
LID - S0378-1135(16)30057-8 [pii]
LID - 10.1016/j.vetmic.2016.03.004 [doi]
AB  - The interferon-induced double-strand RNA activated protein kinase (PKR) plays an 
      important role in antiviral response. The objective of this study was to assess 
      the effect of porcine reproductive and respiratory syndrome virus (PRRSV) on PKR 
      activation. Here we report that PRRSV inhibited PKR activation during its early 
      stage infection of primary pulmonary alveolar macrophages (PAMs). PRRSV infection 
      led to lower level of phosphorylated PKR in comparison with mock-infected cells. 
      The PKR inhibition was sustained until 10h post infection in the presence of 
      polyI:C, a synthetic analog of double-stranded RNA activating PKR. PKR-mediated 
      phosphorylation of the eukaryotic translation initiation factor eIF2alpha was also 
      lower in the PRRSV-infected PAMs during the early stage infection. Interestingly, 
      inactivated PRRSV was capable to inhibit the PKR activation until 6h post 
      infection. This suggests that structural components of PRRSV virions were 
      responsible for the inhibition, although PRRSV replication was needed for longer 
      inhibition. These results indicate that the downregulation of PKR activation 
      during early infection stage should be essential for PRRSV to avoid the antiviral 
      response to initiate replication. This finding contributes to our understanding 
      on PRRSV interaction with host innate immune response and reveal a target for 
      control of PRRSV infection.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Xiao, Yueqiang
AU  - Xiao Y
AD  - Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and 
      Maryland Pathogen Research Institute, University of Maryland, College Park, MD, 
      USA; Shandong Binzhou Animal Science & Veterinary Medicine Academy, Binzhou 
      Branch of Shandong Academy of Agricultural Sciences, Binzhou, Shandong, China.
FAU - Ma, Zexu
AU  - Ma Z
AD  - Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and 
      Maryland Pathogen Research Institute, University of Maryland, College Park, MD, 
      USA.
FAU - Wang, Rong
AU  - Wang R
AD  - Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and 
      Maryland Pathogen Research Institute, University of Maryland, College Park, MD, 
      USA.
FAU - Yang, Liping
AU  - Yang L
AD  - Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and 
      Maryland Pathogen Research Institute, University of Maryland, College Park, MD, 
      USA.
FAU - Nan, Yuchen
AU  - Nan Y
AD  - Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and 
      Maryland Pathogen Research Institute, University of Maryland, College Park, MD, 
      USA.
FAU - Zhang, Yan-Jin
AU  - Zhang YJ
AD  - Molecular Virology Laboratory, VA-MD Regional College of Veterinary Medicine and 
      Maryland Pathogen Research Institute, University of Maryland, College Park, MD, 
      USA. Electronic address: zhangyj@umd.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160307
PL  - Netherlands
TA  - Vet Microbiol
JT  - Veterinary microbiology
JID - 7705469
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - *Down-Regulation
MH  - Enzyme Activation/genetics
MH  - Macrophages, Alveolar/enzymology/immunology/virology
MH  - Phosphorylation
MH  - Poly I-C/immunology
MH  - Porcine Reproductive and Respiratory Syndrome/*enzymology/immunology
MH  - Porcine respiratory and reproductive syndrome virus/*physiology
MH  - Swine
MH  - Virus Replication/physiology
MH  - eIF-2 Kinase/*genetics/*metabolism
OTO - NOTNLM
OT  - Innate immunity
OT  - PKR inhibition
OT  - Porcine reproductive and respiratory syndrome virus (PRRSV)
OT  - Protein kinase PKR
OT  - Pulmonary alveolar macrophages (PAMs)
OT  - eIF2alpha
EDAT- 2016/04/14 06:00
MHDA- 2016/10/14 06:00
CRDT- 2016/04/13 06:00
PHST- 2016/02/02 00:00 [received]
PHST- 2016/03/03 00:00 [revised]
PHST- 2016/03/04 00:00 [accepted]
PHST- 2016/04/13 06:00 [entrez]
PHST- 2016/04/14 06:00 [pubmed]
PHST- 2016/10/14 06:00 [medline]
AID - S0378-1135(16)30057-8 [pii]
AID - 10.1016/j.vetmic.2016.03.004 [doi]
PST - ppublish
SO  - Vet Microbiol. 2016 May 1;187:1-7. doi: 10.1016/j.vetmic.2016.03.004. Epub 2016 
      Mar 7.