Huiyuan Jing , Ying Liu , Yvzhen Song , Tao Song , Ting Wang , Zhen Ding , Jie Liu , Pandeng Zhao
{"title":"ZDHHC3-LYPLA1通过可逆棕榈酰化调控PRRSV-2复制。","authors":"Huiyuan Jing , Ying Liu , Yvzhen Song , Tao Song , Ting Wang , Zhen Ding , Jie Liu , Pandeng Zhao","doi":"10.1016/j.vetmic.2025.110368","DOIUrl":null,"url":null,"abstract":"<div><div>Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious swine pathogen, causing respiratory problems in piglets and reproductive failure in sows. Palmitoylation, catalyzed by zinc finger Asp-His-His-Cys (ZDHHC) domain-containing palmitoyl acyltransferases, plays intricate roles in virus infection. However, whether palmitoylation regulates PRRSV replication is incompletely understood. Here, we report that inhibition of palmitoylation by 2-bromo palmitate (2-BP) promotes PRRSV multiplication. ZDHHC3 is identified as the key palmitoyl transferase regulating PRRSV replication in PAMs infection. Mechanistically, ZDHHC3 catalyzes nucleocapsid (N) protein palmitoylation at cysteine 90. This modification prevents the Nsp9-N protein interaction and subsequent viral RNA synthesis. Furthermore, LYPLA1 de-palmitoylates N protein, thus counteracting the ZDHHC3’s activity on PRRSV replication. Meanwhile, the administration of small-molecule inhibitor ML348 targeting LYPLA1 could hinder PRRSV-2 replication. In summary, our results underscore the critical role of reversible palmitoylation in PRRSV replication. These findings might provide potential new anti-PRRSV strategies.</div></div>","PeriodicalId":23551,"journal":{"name":"Veterinary microbiology","volume":"301 ","pages":"Article 110368"},"PeriodicalIF":2.4000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"ZDHHC3-LYPLA1 regulates PRRSV-2 replication through reversible palmitoylation\",\"authors\":\"Huiyuan Jing , Ying Liu , Yvzhen Song , Tao Song , Ting Wang , Zhen Ding , Jie Liu , Pandeng Zhao\",\"doi\":\"10.1016/j.vetmic.2025.110368\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious swine pathogen, causing respiratory problems in piglets and reproductive failure in sows. Palmitoylation, catalyzed by zinc finger Asp-His-His-Cys (ZDHHC) domain-containing palmitoyl acyltransferases, plays intricate roles in virus infection. However, whether palmitoylation regulates PRRSV replication is incompletely understood. Here, we report that inhibition of palmitoylation by 2-bromo palmitate (2-BP) promotes PRRSV multiplication. ZDHHC3 is identified as the key palmitoyl transferase regulating PRRSV replication in PAMs infection. Mechanistically, ZDHHC3 catalyzes nucleocapsid (N) protein palmitoylation at cysteine 90. This modification prevents the Nsp9-N protein interaction and subsequent viral RNA synthesis. Furthermore, LYPLA1 de-palmitoylates N protein, thus counteracting the ZDHHC3’s activity on PRRSV replication. Meanwhile, the administration of small-molecule inhibitor ML348 targeting LYPLA1 could hinder PRRSV-2 replication. In summary, our results underscore the critical role of reversible palmitoylation in PRRSV replication. These findings might provide potential new anti-PRRSV strategies.</div></div>\",\"PeriodicalId\":23551,\"journal\":{\"name\":\"Veterinary microbiology\",\"volume\":\"301 \",\"pages\":\"Article 110368\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary microbiology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378113525000033\",\"RegionNum\":2,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary microbiology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378113525000033","RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
ZDHHC3-LYPLA1 regulates PRRSV-2 replication through reversible palmitoylation
Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious swine pathogen, causing respiratory problems in piglets and reproductive failure in sows. Palmitoylation, catalyzed by zinc finger Asp-His-His-Cys (ZDHHC) domain-containing palmitoyl acyltransferases, plays intricate roles in virus infection. However, whether palmitoylation regulates PRRSV replication is incompletely understood. Here, we report that inhibition of palmitoylation by 2-bromo palmitate (2-BP) promotes PRRSV multiplication. ZDHHC3 is identified as the key palmitoyl transferase regulating PRRSV replication in PAMs infection. Mechanistically, ZDHHC3 catalyzes nucleocapsid (N) protein palmitoylation at cysteine 90. This modification prevents the Nsp9-N protein interaction and subsequent viral RNA synthesis. Furthermore, LYPLA1 de-palmitoylates N protein, thus counteracting the ZDHHC3’s activity on PRRSV replication. Meanwhile, the administration of small-molecule inhibitor ML348 targeting LYPLA1 could hinder PRRSV-2 replication. In summary, our results underscore the critical role of reversible palmitoylation in PRRSV replication. These findings might provide potential new anti-PRRSV strategies.
期刊介绍：
Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal.
Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge.
Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.
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