PRRSV alters m6A methylation and alternative splicing to regulate immune, extracellular matrix-associated function

Chenghong Lin; Mu Zeng; Jia Song; Hua Li; Zheng Feng; Kui Li; Yangli Pei

doi:10.1016/j.ijbiomac.2023.126741

PRRSV alters m⁶A methylation and alternative splicing to regulate immune, extracellular matrix-associated function

Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126741. doi: 10.1016/j.ijbiomac.2023.126741. Epub 2023 Sep 9.

Authors

Chenghong Lin¹, Mu Zeng¹, Jia Song¹, Hua Li¹, Zheng Feng¹, Kui Li², Yangli Pei³

Affiliations

¹ 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.
² 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.
³ 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.

PMID: 37696370
DOI: 10.1016/j.ijbiomac.2023.126741

Abstract

The alternative splicing and N6-methyladenosine (m⁶A) 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 GSK3β 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.

Keywords: Alternative splicing; N6-methyladenosine; PRRSV.

MeSH terms

Alternative Splicing / genetics
Animals
Gene Expression Profiling
Methylation
Porcine Reproductive and Respiratory Syndrome*
Porcine respiratory and reproductive syndrome virus* / genetics
Swine