PMID- 31738790
OWN - NLM
STAT- MEDLINE
DCOM- 20200304
LR  - 20211204
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 15
IP  - 11
DP  - 2019 Nov
TI  - Reprogramming the unfolded protein response for replication by porcine 
      reproductive and respiratory syndrome virus.
PG  - e1008169
LID - 10.1371/journal.ppat.1008169 [doi]
LID - e1008169
AB  - The unfolded protein response (UPR) in the endoplasmic reticulum (ER) constitutes 
      a critical component of host innate immunity against microbial infections. In 
      this report, we show that porcine reproductive and respiratory syndrome virus 
      (PRRSV) utilizes the UPR machinery for its own benefit. We provide evidence that 
      the virus targets the UPR central regulator GRP78 for proteasomal degradation via 
      a mechanism that requires viral glycoprotein GP2a, while both IRE1-XBP1s and 
      PERK-eIF2alpha-ATF4 signaling branches of the UPR are turned on at early stage of 
      infection. The activated effector XBP1s was found to enter the nucleus, but ATF4 
      was unexpectedly diverted to cytoplasmic viral replication complexes by means of 
      nonstructural proteins nsp2/3 to promote viral RNA synthesis. RNAi knockdown of 
      either ATF4 or XBP1s dramatically attenuated virus titers, while overexpression 
      caused increases. These observations reveal attractive host targets (e.g., ATF4 
      and XBP1s) for antiviral drugs and have implications in vaccine development.
FAU - Gao, Peng
AU  - Gao P
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Chai, Yue
AU  - Chai Y
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Song, Jiangwei
AU  - Song J
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Liu, Teng
AU  - Liu T
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Chen, Peng
AU  - Chen P
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Zhou, Lei
AU  - Zhou L
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Ge, Xinna
AU  - Ge X
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Guo, Xin
AU  - Guo X
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Han, Jun
AU  - Han J
AUID- ORCID: 0000-0002-7104-7223
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
FAU - Yang, Hanchun
AU  - Yang H
AUID- ORCID: 0000-0003-3359-3925
AD  - Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural 
      Affairs, China Agricultural University College of Veterinary Medicine, Beijing, 
      People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191118
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (X-Box Binding Protein 1)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Activating Transcription Factor 4/genetics/metabolism
MH  - Animals
MH  - Endoplasmic Reticulum/metabolism/*virology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Heat-Shock Proteins/genetics/metabolism
MH  - Porcine Reproductive and Respiratory Syndrome/genetics/metabolism/*virology
MH  - Porcine respiratory and reproductive syndrome virus/*physiology
MH  - Signal Transduction
MH  - Swine
MH  - *Unfolded Protein Response
MH  - *Virus Replication
MH  - X-Box Binding Protein 1/genetics/metabolism
MH  - eIF-2 Kinase/genetics/*metabolism
PMC - PMC6932825
COIS- NO authors have competing interests.
EDAT- 2019/11/19 06:00
MHDA- 2020/03/05 06:00
PMCR- 2019/11/18
CRDT- 2019/11/19 06:00
PHST- 2019/05/03 00:00 [received]
PHST- 2019/10/29 00:00 [accepted]
PHST- 2019/12/26 00:00 [revised]
PHST- 2019/11/19 06:00 [pubmed]
PHST- 2020/03/05 06:00 [medline]
PHST- 2019/11/19 06:00 [entrez]
PHST- 2019/11/18 00:00 [pmc-release]
AID - PPATHOGENS-D-19-00844 [pii]
AID - 10.1371/journal.ppat.1008169 [doi]
PST - epublish
SO  - PLoS Pathog. 2019 Nov 18;15(11):e1008169. doi: 10.1371/journal.ppat.1008169. 
      eCollection 2019 Nov.