PMID- 31189711
OWN - NLM
STAT- MEDLINE
DCOM- 20200602
LR  - 20200602
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 93
IP  - 17
DP  - 2019 Sep 1
TI  - Porcine Reproductive and Respiratory Syndrome Virus Activates Lipophagy To 
      Facilitate Viral Replication through Downregulation of NDRG1 Expression.
LID - 10.1128/JVI.00526-19 [doi]
LID - e00526-19
AB  - Autophagy maintains cellular homeostasis by degrading organelles, proteins, and 
      lipids in lysosomes. Autophagy is involved in the innate and adaptive immune 
      responses to a variety of pathogens. Some viruses can hijack host autophagy to 
      enhance their replication. However, the role of autophagy in porcine reproductive 
      and respiratory syndrome virus (PRRSV) infection is unclear. Here, we show that 
      N-Myc downstream-regulated gene 1 (NDRG1) deficiency induced autophagy, which 
      facilitated PRRSV replication by regulating lipid metabolism. NDRG1 mRNA is 
      expressed ubiquitously in most porcine tissues and most strongly in white adipose 
      tissue. PRRSV infection downregulated the expression of NDRG1 mRNA and protein, 
      while NDRG1 deficiency contributed to PRRSV RNA replication and progeny virus 
      assembly. NDRG1 deficiency reduced the number of intracellular lipid droplets 
      (LDs), but the expression levels of key genes in lipogenesis and lipolysis were 
      not altered. Our results also show that NDRG1 deficiency promoted autophagy and 
      increased the subsequent yields of hydrolyzed free fatty acids (FFAs). The 
      reduced LD numbers, increased FFA levels, and enhanced PRRSV replication were 
      abrogated in the presence of an autophagy inhibitor. Overall, our findings 
      suggest that NDRG1 plays a negative role in PRRSV replication by suppressing 
      autophagy and LD degradation.IMPORTANCE Porcine reproductive and respiratory 
      syndrome virus (PRRSV), an enveloped single-positive-stranded RNA virus, causes 
      acute respiratory distress in piglets and reproductive failure in sows. It has 
      led to tremendous economic losses in the swine industry worldwide since it was 
      first documented in the late 1980s. Vaccination is currently the major strategy 
      used to control the disease. However, conventional vaccines and other strategies 
      do not provide satisfactory or sustainable prevention. Therefore, safe and 
      effective strategies to control PRRSV are urgently required. The significance of 
      our research is that we demonstrate a previously unreported relationship between 
      PRRSV, NDRG1, and lipophagy in the context of viral infection. Furthermore, our 
      data point to a new role for NDRG1 in autophagy and lipid metabolism. Thus, NDRG1 
      and lipophagy will have significant implications for understanding PRRSV 
      pathogenesis for developing new therapeutics.
CI  - Copyright (c) 2019 Wang et al.
FAU - Wang, Jiang
AU  - Wang J
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Liu, Jiao-Yang
AU  - Liu JY
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Shao, Ke-Yu
AU  - Shao KY
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Han, Ying-Qian
AU  - Han YQ
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Li, Guo-Li
AU  - Li GL
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Ming, Sheng-Li
AU  - Ming SL
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Su, Bing-Qian
AU  - Su BQ
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Du, Yong-Kun
AU  - Du YK
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Liu, Zhong-Hu
AU  - Liu ZH
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Zhang, Gai-Ping
AU  - Zhang GP
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China.
FAU - Yang, Guo-Yu
AU  - Yang GY
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China 
      haubiochem@163.com chubeibei_hau@hotmail.com.
FAU - Chu, Bei-Bei
AU  - Chu BB
AD  - College of Animal Sciences and Veterinary Medicine, Henan Agricultural 
      University, Zhengzhou, Henan Province, People's Republic of China 
      haubiochem@163.com chubeibei_hau@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190813
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (N-myc downstream-regulated gene 1 protein)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Cell Cycle Proteins/*genetics/*metabolism
MH  - *Down-Regulation
MH  - Fatty Acids, Nonesterified/*chemistry
MH  - HEK293 Cells
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics/*metabolism
MH  - Male
MH  - Phylogeny
MH  - Porcine Reproductive and Respiratory Syndrome/genetics/metabolism/*virology
MH  - Porcine respiratory and reproductive syndrome virus/pathogenicity/*physiology
MH  - Swine
MH  - Virus Replication
PMC - PMC6694807
OTO - NOTNLM
OT  - N-Myc downstream-regulated gene 1
OT  - autophagy
OT  - lipid droplet
OT  - lipophagy
OT  - porcine reproductive and respiratory syndrome virus
EDAT- 2019/06/14 06:00
MHDA- 2020/06/03 06:00
PMCR- 2019/08/13
CRDT- 2019/06/14 06:00
PHST- 2019/03/30 00:00 [received]
PHST- 2019/06/05 00:00 [accepted]
PHST- 2019/06/14 06:00 [pubmed]
PHST- 2020/06/03 06:00 [medline]
PHST- 2019/06/14 06:00 [entrez]
PHST- 2019/08/13 00:00 [pmc-release]
AID - JVI.00526-19 [pii]
AID - 00526-19 [pii]
AID - 10.1128/JVI.00526-19 [doi]
PST - epublish
SO  - J Virol. 2019 Aug 13;93(17):e00526-19. doi: 10.1128/JVI.00526-19. Print 2019 Sep 
      1.