PMID- 31835577 OWN - NLM STAT- MEDLINE DCOM- 20200924 LR - 20200924 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 11 IP - 12 DP - 2019 Dec 10 TI - Fatty Acids Regulate Porcine Reproductive and Respiratory Syndrome Virus Infection via the AMPK-ACC1 Signaling Pathway. LID - 10.3390/v11121145 [doi] LID - 1145 AB - Lipids play a crucial role in the replication of porcine reproductive and respiratory syndrome virus (PRRSV), a porcine virus that is endemic throughout the world. However, little is known about the effect of fatty acids (FAs), a type of vital lipid, on PRRSV infection. In this study, we found that treatment with a FA biosynthetic inhibitor significantly inhibited PRRSV propagation, indicating the necessity of FAs for optimal replication of PRRSV. Further study revealed that 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK), a key kinase antagonizing FA biosynthesis, was strongly activated by PRRSV and the pharmacological activator of AMPK exhibited anti-PRRSV activity. Additionally, we found that acetyl-CoA carboxylase 1 (ACC1), the first rate-limiting enzyme in the FA biosynthesis pathway, was phosphorylated (inactive form) by PRRSV-activated AMPK, and active ACC1 was required for PRRSV proliferation, suggesting that the PRRSV infection induced the activation of the AMPK-ACC1 pathway, which was not conducive to PRRSV replication. This work provides new evidence about the mechanisms involved in host lipid metabolism during PRRSV infection and identifies novel potential antiviral targets for PRRSV. FAU - Long, Siwen AU - Long S AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Zhou, Yanrong AU - Zhou Y AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Bai, Dongcheng AU - Bai D AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Hao, Wanjun AU - Hao W AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Zheng, Bohan AU - Zheng B AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Xiao, Shaobo AU - Xiao S AUID- ORCID: 0000-0003-0023-9188 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Fang, Liurong AU - Fang L AUID- ORCID: 0000-0003-1406-6409 AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China. AD - The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. AD - Laboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, 1 Shi-zi-shan Street, Wuhan 430070, Hubei, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191210 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Fatty Acids) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - EC 6.4.1.2 (Acetyl-CoA Carboxylase) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Acetyl-CoA Carboxylase/*metabolism MH - Animals MH - Biosynthetic Pathways/drug effects MH - Fatty Acids/*metabolism MH - *Host-Pathogen Interactions MH - Models, Biological MH - Porcine Reproductive and Respiratory Syndrome/*metabolism/*virology MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Signal Transduction MH - Swine MH - Virus Replication PMC - PMC6950460 OTO - NOTNLM OT - AMP-activated protein kinase (AMPK) OT - acetyl-CoA carboxylase 1 (ACC1) OT - fatty acid OT - porcine reproductive and respiratory syndrome virus (PRRSV) COIS- The authors declare no conflicts of interest. EDAT- 2019/12/15 06:00 MHDA- 2020/09/25 06:00 PMCR- 2019/12/01 CRDT- 2019/12/15 06:00 PHST- 2019/10/25 00:00 [received] PHST- 2019/12/06 00:00 [revised] PHST- 2019/12/08 00:00 [accepted] PHST- 2019/12/15 06:00 [entrez] PHST- 2019/12/15 06:00 [pubmed] PHST- 2020/09/25 06:00 [medline] PHST- 2019/12/01 00:00 [pmc-release] AID - v11121145 [pii] AID - viruses-11-01145 [pii] AID - 10.3390/v11121145 [doi] PST - epublish SO - Viruses. 2019 Dec 10;11(12):1145. doi: 10.3390/v11121145.