PMID- 37454810 OWN - NLM STAT- MEDLINE DCOM- 20231026 LR - 20231112 IS - 1995-820X (Electronic) IS - 1674-0769 (Print) IS - 1995-820X (Linking) VI - 38 IP - 5 DP - 2023 Oct TI - miR-204 suppresses porcine reproductive and respiratory syndrome virus (PRRSV) replication via inhibiting LC3B-mediated autophagy. PG - 690-698 LID - S1995-820X(23)00084-6 [pii] LID - 10.1016/j.virs.2023.07.004 [doi] AB - Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) has been regarded as a persistent challenge for the swine farms worldwide. microRNAs (miRNAs) play key roles in regulating almost every important biological process, including virus-host interaction. In this study, we found that miR-204 was highly expressed in cells that were not permissive to PRRSV infection compared with cells susceptible to PRRSV infection. Subsequently, we demonstrated that overexpression of miR-204 significantly inhibited PRRSV replication in porcine alveolar macrophages (PAMs). Through bioinformatic analysis, we found that there existed a potential binding site of miR-204 on the 3'UTR of microtubule associated protein 1 light chain 3B (MAP1LC3B, LC3B), a hallmark of autophagy. Applying experiments including luciferase reporter assay and UV cross-linking and immunoprecipitation (CLIP) assay, we demonstrated that miR-204 directly targeted LC3B, thereby downregulating autophagy. Meanwhile, we investigated the interplay between autophagy and PRRSV replication in PAMs, confirming that PRRSV infection induces autophagy, which in turn facilitates viral replication. Overall, we verify that miR-204 suppresses PRRSV replication via inhibiting LC3B-mediated autophagy in PAMs. These findings will provide a novel potential approach for us to develop antiviral therapeutic agents and controlling measures for future PRRSV outbreaks. CI - Copyright (c) 2023 The Authors. Publishing services by Elsevier B.V. All rights reserved. FAU - Yao, Yao AU - Yao Y AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. FAU - Li, Sihan AU - Li S AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. FAU - Zhu, Yingqi AU - Zhu Y AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. FAU - Xu, Yangyang AU - Xu Y AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. FAU - Hao, Siyuan AU - Hao S AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. FAU - Guo, Shuyuan AU - Guo S AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. FAU - Feng, Wen-Hai AU - Feng WH AD - State Key Laboratory of Animal Biotech Breeding, Frontiers Science Center for Molecular Design Breeding, Ministry of Agriculture Key Laboratory of Soil Microbiology, and Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. Electronic address: whfeng@cau.edu.cn. LA - eng PT - Journal Article DEP - 20230716 PL - Netherlands TA - Virol Sin JT - Virologica Sinica JID - 101514185 RN - 0 (MicroRNAs) SB - IM MH - Swine MH - Animals MH - *Porcine respiratory and reproductive syndrome virus/genetics MH - *Porcine Reproductive and Respiratory Syndrome/genetics MH - Cell Line MH - *MicroRNAs/genetics/metabolism MH - Virus Replication MH - Autophagy/genetics PMC - PMC10590697 OTO - NOTNLM OT - Autophagy OT - LC3B OT - Porcine reproductive and respiratory syndrome virus (PRRSV) OT - miR-204 COIS- Conflict of interest Prof. Wenhai Feng is an Editorial Board member for Virologica Sinica and was not involved in the editorial review or the decision to publish this article. The authors declare that they have no conflict of interest. EDAT- 2023/07/17 00:42 MHDA- 2023/10/26 06:42 PMCR- 2023/07/16 CRDT- 2023/07/16 19:25 PHST- 2023/04/07 00:00 [received] PHST- 2023/07/07 00:00 [accepted] PHST- 2023/10/26 06:42 [medline] PHST- 2023/07/17 00:42 [pubmed] PHST- 2023/07/16 19:25 [entrez] PHST- 2023/07/16 00:00 [pmc-release] AID - S1995-820X(23)00084-6 [pii] AID - 10.1016/j.virs.2023.07.004 [doi] PST - ppublish SO - Virol Sin. 2023 Oct;38(5):690-698. doi: 10.1016/j.virs.2023.07.004. Epub 2023 Jul 16.