PMID- 33002680 OWN - NLM STAT- MEDLINE DCOM- 20210712 LR - 20210712 IS - 1873-2542 (Electronic) IS - 0378-1135 (Print) IS - 0378-1135 (Linking) VI - 250 DP - 2020 Nov TI - Polyamine regulation of porcine reproductive and respiratory syndrome virus infection depends on spermidine-spermine acetyltransferase 1. PG - 108839 LID - S0378-1135(20)30977-9 [pii] LID - 10.1016/j.vetmic.2020.108839 [doi] AB - Like obligate intracellular parasites, viruses co-opt host cell resources to establish productive infections. Polyamines are key aliphatic molecules that perform important roles in cellular growth and proliferation. They are also needed for the successful multiplication of various viruses. Little is known about the effects of polyamines on Arteriviridae infections. Here, porcine reproductive and respiratory syndrome virus (PRRSV), an economically prominent porcine virus, was used to investigate virus-polyamine interactions. We found that PRRSV infection significantly downregulated the levels of cellular polyamines. Using an inhibitor or specific short interfering RNAs (siRNAs) of ornithine decarboxylase 1, a key anabolic enzyme involved in the classical de novo biosynthesis of polyamines, we found that polyamine depletion abrogated PRRSV proliferation, and this effect was recoverable by adding exogenous spermidine and spermine, but not putrescine to the cells, suggesting that the host inhibits polyamine biosynthesis to restrict PRRSV proliferation. Further analysis revealed that the expression level of spermidine-spermine acetyltransferase 1 (SAT1), a catabolic enzyme that reduces spermidine and spermine levels, was upregulated during PRRSV infection, but conversely, SAT1 had an inhibitory effect on PRRSV reproduction. Our data show that polyamines are important molecules during PRRSV-host interactions, and polyamines and their biosynthetic pathways are potential therapeutic targets against PRRSV infection. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Zhou, Yanrong AU - Zhou Y AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Hou, Zhenzhen AU - Hou Z AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Fang, Liurong AU - Fang L AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Ke, Qiyun AU - Ke Q AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Xiong, Yujian AU - Xiong Y AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Fang, Puxian AU - Fang P AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. FAU - Xiao, Shaobo AU - Xiao S AD - State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China. Electronic address: vet@mail.hzau.edu.cn. LA - eng PT - Journal Article DEP - 20200919 PL - Netherlands TA - Vet Microbiol JT - Veterinary microbiology JID - 7705469 RN - 0 (Polyamines) RN - 2FZ7Y3VOQX (Spermine) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.57 (diamine N-acetyltransferase) RN - U87FK77H25 (Spermidine) SB - IM MH - Acetyltransferases/*genetics/metabolism MH - Animals MH - Cell Line MH - Down-Regulation MH - Gene Expression Regulation MH - *Host Microbial Interactions MH - Kidney/cytology MH - Polyamines/*metabolism MH - Porcine respiratory and reproductive syndrome virus/*physiology MH - Spermidine/*metabolism MH - Spermine/*metabolism MH - Swine MH - Up-Regulation MH - Virus Replication PMC - PMC7501835 OTO - NOTNLM OT - Antiviral drug target OT - Polyamine OT - Porcine reproductive and respiratory syndrome virus OT - Spermidine-spermine acetyltransferase 1 COIS- The authors declare that there are no conflicts of interest. EDAT- 2020/10/02 06:00 MHDA- 2021/07/13 06:00 PMCR- 2020/09/19 CRDT- 2020/10/01 20:13 PHST- 2020/06/03 00:00 [received] PHST- 2020/08/31 00:00 [accepted] PHST- 2020/10/02 06:00 [pubmed] PHST- 2021/07/13 06:00 [medline] PHST- 2020/10/01 20:13 [entrez] PHST- 2020/09/19 00:00 [pmc-release] AID - S0378-1135(20)30977-9 [pii] AID - 108839 [pii] AID - 10.1016/j.vetmic.2020.108839 [doi] PST - ppublish SO - Vet Microbiol. 2020 Nov;250:108839. doi: 10.1016/j.vetmic.2020.108839. Epub 2020 Sep 19.