PMID- 37696370 OWN - NLM STAT- MEDLINE DCOM- 20231123 LR - 20231123 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 253 IP - Pt 2 DP - 2023 Dec 31 TI - PRRSV alters m(6)A methylation and alternative splicing to regulate immune, extracellular matrix-associated function. PG - 126741 LID - S0141-8130(23)03638-3 [pii] LID - 10.1016/j.ijbiomac.2023.126741 [doi] AB - The alternative splicing and N6-methyladenosine (m(6)A) modifications occurring during porcine reproductive and respiratory syndrome virus (PRRSV) infections remain poorly understood. Transcriptome and MeRIP-seq analyses were performed to identify the gene expression changes, splicing and m6A modifications in the lungs of PRRSV-infected pigs. In total, 1624 differentially expressed genes (DEGs) were observed between PRRSV-infected and uninfected pigs. We observed significant alterations in alternative splicing (54,367 events) and m6A modifications (2265 DASEs) in numerous genes, including LMO7, SLC25A27, ZNF185, and ECM1, during PRRSV infection. LMO7 and ZNF185 exhibited alternative splicing variants and reduced mRNA expression levels following PRRSV infection. Notably, LMO7 inhibited c-JUN, SMAD3, and FAK expression, whereas ZNF185 affected the expression of FAK, CDH1, and GSK3beta downstream. Additionally, ECM1 influenced FAK expression by targeting ITGB3 and AKT2, suggesting its involvement in extracellular matrix accumulation through the ITGB3-AKT2/FAK pathway. These changes may facilitate viral invasion and replication by modulating the expression of genes and proteins participating in crucial cellular processes associated with immunity and the extracellular matrix. We highlight the importance of these genes and their associated pathways in PRRSV infections and suggest that targeting these may be a promising therapeutic approach for treating viral infections. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Lin, Chenghong AU - Lin C AD - Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan 528225, China. FAU - Zeng, Mu AU - Zeng M AD - Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan 528225, China. FAU - Song, Jia AU - Song J AD - Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan 528225, China. FAU - Li, Hua AU - Li H AD - Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan 528225, China. FAU - Feng, Zheng AU - Feng Z AD - Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan 528225, China. FAU - Li, Kui AU - Li K AD - Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, China. Electronic address: likui@caas.cn. FAU - Pei, Yangli AU - Pei Y AD - Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Key Laboratory of Animal Molecular Design and Precise Breeding of Guangdong Higher Education Institutes, School of Life Science and Engineering, Foshan University, Foshan 528225, China. Electronic address: peiyl@fosu.edu.cn. LA - eng PT - Journal Article DEP - 20230909 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 SB - IM MH - Swine MH - Animals MH - *Porcine respiratory and reproductive syndrome virus/genetics MH - *Porcine Reproductive and Respiratory Syndrome MH - Gene Expression Profiling MH - Methylation MH - Alternative Splicing/genetics OTO - NOTNLM OT - Alternative splicing OT - N6-methyladenosine OT - PRRSV COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/09/12 00:42 MHDA- 2023/11/23 06:42 CRDT- 2023/09/11 19:18 PHST- 2022/11/17 00:00 [received] PHST- 2023/08/07 00:00 [revised] PHST- 2023/08/25 00:00 [accepted] PHST- 2023/11/23 06:42 [medline] PHST- 2023/09/12 00:42 [pubmed] PHST- 2023/09/11 19:18 [entrez] AID - S0141-8130(23)03638-3 [pii] AID - 10.1016/j.ijbiomac.2023.126741 [doi] PST - ppublish SO - Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126741. doi: 10.1016/j.ijbiomac.2023.126741. Epub 2023 Sep 9.