Global Analysis of Alternative Splicing Difference in Peripheral Immune Organs between Tongcheng Pigs and Large White Pigs Artificially Infected with PRRSV In Vivo

Abstract

Alternative splicing (AS) plays a significant role in regulating gene expression at the transcriptional level in eukaryotes. Flexibility and diversity of transcriptome and proteome can be significantly increased through alternative splicing of genes. In the present study, transcriptome data of peripheral immune organs including spleen and inguinal lymph nodes (ILN) were used to identify AS difference between PRRSV-resistant Tongcheng (TC) pigs and PRRSV-susceptible Large White (LW) pigs artificially infected with porcine reproductive and respiratory syndrome virus (PRRSV) in vivo. The results showed that PRRSV infection induced global alternative splicing events (ASEs) with different modes. Among them, 373 genes and 595 genes in the spleen and ILN of TC pigs, while 458 genes and 560 genes in the spleen and ILN of LW pigs had significantly differential ASEs. Alternative splicing was subject to tissue-specific and lineage-specific regulation in response to PRRSV infection. Enriched GO terms and pathways showed that genes with differential ASEs played important roles in transcriptional regulation, immune response, metabolism, and apoptosis. Furthermore, a splicing factor associated with apoptosis, SRSF4, was significantly upregulated in LW pigs. Functional analysis on apoptosis associated genes was validated by RT-PCR and DNA sequencing. These findings revealed different response to PRRSV between PRRSV-resistant TC pigs and PRRSV-susceptible LW pigs at the level of alternative splicing, suggesting the potential relationship between AS and disease resistance to PRRSV.