PMID- 37217033
OWN - NLM
STAT- MEDLINE
DCOM- 20230619
LR  - 20231116
IS  - 1872-7492 (Electronic)
IS  - 0168-1702 (Print)
IS  - 0168-1702 (Linking)
VI  - 333
DP  - 2023 Aug
TI  - Porcine reproductive and respiratory syndrome virus regulates lipid droplet 
      accumulation in lipid metabolic pathways to promote viral replication.
PG  - 199139
LID - S0168-1702(23)00101-6 [pii]
LID - 10.1016/j.virusres.2023.199139 [doi]
LID - 199139
AB  - Porcine reproductive and respiratory syndrome (PRRS) is a severe respiratory 
      disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) 
      that can lead to the abortion of pregnant sows and decreased boar semen quality. 
      However, the mechanisms of PRRSV replication in the host have not yet been fully 
      elucidated. As lipid metabolism and lipid droplets (LDs) have been reported to 
      play important roles in the replication of various viruses, we aimed to explore 
      the mechanisms through which LDs affect PRRSV replication. Laser confocal and 
      transmission electron microscopy revealed that PRRSV infection promoted 
      intracellular LD accumulation, which was significantly reduced by treatment with 
      the NF-kappaB signaling pathway inhibitors BAY11-7082 and metformin hydrochloride 
      (MH). In addition, treatment with a DGAT1 inhibitor significantly reduced the 
      protein expression of Phosphorylated NF-KappaB P65and PIkappaB and the transcription of 
      IL-1beta and IL-8 in the NF-kappaB signaling pathway. Furthermore, we showed that the 
      reduction of the NF-kappaB signaling pathway and LDs significantly reduced PRRSV 
      replication. Together, the findings of this study suggest a novel mechanism 
      through which PRRSV regulates the NF-kappaB signaling pathway to increase LD 
      accumulation and promote viral replication. Moreover, we demonstrated that both 
      BAY11-7082 and MH can reduce PRRSV replication by reducing the NF-kappaB signaling 
      pathway and LD accumulation. This study lays a theoretical foundation for 
      research on the mechanism of PRRS prevention and control, as well as the research 
      and development of antiviral drugs.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Yang, Yunlong
AU  - Yang Y
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 
      Maoming 525000, China.
FAU - Luo, Yizhuo
AU  - Luo Y
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 
      Maoming 525000, China.
FAU - Yi, Songqiang
AU  - Yi S
AD  - Agricultural Technology Extension Center of Jiangxi Province, Nanchang, China.
FAU - Gao, Qi
AU  - Gao Q
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 
      Maoming 525000, China.
FAU - Gong, Ting
AU  - Gong T
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and 
      Rural Affairs, PR China.
FAU - Feng, Yongzhi
AU  - Feng Y
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China.
FAU - Wu, Dongdong
AU  - Wu D
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and 
      Rural Affairs, PR China.
FAU - Zheng, Xiaoyu
AU  - Zheng X
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and 
      Rural Affairs, PR China.
FAU - Wang, Heng
AU  - Wang H
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 
      Maoming 525000, China.
FAU - Zhang, Guihong
AU  - Zhang G
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 
      Maoming 525000, China; Key Laboratory of Animal Vaccine Development, Ministry of 
      Agriculture and Rural Affairs, PR China.
FAU - Sun, Yankuo
AU  - Sun Y
AD  - Guangdong Provincial Key Laboratory of Zoonosis Prevention and Control, College 
      of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR 
      China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, 
      Maoming 525000, China; Key Laboratory of Animal Vaccine Development, Ministry of 
      Agriculture and Rural Affairs, PR China. Electronic address: 
      yankuosun@scau.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230607
PL  - Netherlands
TA  - Virus Res
JT  - Virus research
JID - 8410979
RN  - 0 (NF-kappa B)
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Lipids)
SB  - IM
MH  - Swine
MH  - Animals
MH  - Male
MH  - Female
MH  - *Porcine respiratory and reproductive syndrome virus/metabolism
MH  - *Porcine Reproductive and Respiratory Syndrome
MH  - NF-kappa B/metabolism
MH  - Lipid Droplets/metabolism
MH  - Semen Analysis
MH  - Cell Line
MH  - Virus Replication
MH  - Lipids
PMC - PMC10352717
OTO - NOTNLM
OT  - Lipid droplet
OT  - Lipid metabolism
OT  - Nf-kappab signaling pathway
OT  - PRRSV
COIS- Declaration of Competing Interest The authors declare that the research was 
      conducted in the absence of any commercial or financial relationships that could 
      be construed as a potential conflict of interest.
EDAT- 2023/05/23 01:06
MHDA- 2023/06/19 13:08
PMCR- 2023/06/07
CRDT- 2023/05/22 19:19
PHST- 2023/02/11 00:00 [received]
PHST- 2023/05/16 00:00 [revised]
PHST- 2023/05/19 00:00 [accepted]
PHST- 2023/06/19 13:08 [medline]
PHST- 2023/05/23 01:06 [pubmed]
PHST- 2023/05/22 19:19 [entrez]
PHST- 2023/06/07 00:00 [pmc-release]
AID - S0168-1702(23)00101-6 [pii]
AID - 199139 [pii]
AID - 10.1016/j.virusres.2023.199139 [doi]
PST - ppublish
SO  - Virus Res. 2023 Aug;333:199139. doi: 10.1016/j.virusres.2023.199139. Epub 2023 
      Jun 7.