Global Mapping of H3K4 Trimethylation (H3K4me3) and Transcriptome Analysis Reveal Genes Involved in the Response to Epidemic Diarrhea Virus Infections in Pigs

Abstract

Porcine epidemic diarrhea virus (PEDV) is currently detected as the main pathogen causing severe diarrhea in pig farms. The phenotypic alterations induced by pathogenic infections are usually tightly linked with marked changes in epigenetic modification and gene expression. We performed global mapping of H3K4 trimethylation (H3K4me3) and transcriptomic analyses in the jejunum of PEDV-infected and healthy piglets using chromatin immunoprecipitation sequencing and RNA-seq techniques. A total of 1885 H3K4me3 peaks that are associated with 1723 genes were characterized. Moreover, 290 differentially expressed genes were identified, including 104 up-regulated and 186 down-regulated genes. Several antiviral genes including 2’-5’-oligoadenylate synthetase 1 (OAS1), 2’-5’-oligoadenylate synthetase 2 (OAS2), ephrin B2 (EFNB2), and CDC28 protein kinase regulatory subunit 1B (CKS1B) with higher H3K4me3 enrichment and expression levels in PEDV-infected samples suggested the potential roles of H3K4me3 deposition in promoting their expressions. Transcription factor annotation analysis highlighted the potential roles of two transcription factors interferon regulatory factor 8 (IRF8) and Kruppel like factor 4 (KLF4) in modulating the differential expression of genes involved in PEDV infection. The results provided novel insights into PEDV infection from the transcriptomic and epigenetic layers and revealed previously unknown and intriguing elements potentially involved in the host responses.

Transcriptome analysis reveals modulation of the STAT family in PEDV-infected IPEC-J2 cells

“…With this in mind, we believe that more integrated and detailed studies of time-resolved or even single-cell-resolved gene expression changes will aid in understanding the host gene response to PEDV infection. A recent study performed global mapping of H3K4 trimethylation and transcriptomic analyses in the PEDV-infected jejunum of piglets compared with healthy piglets, using chromatin immunoprecipitation sequencing and RNA-seq, and provided novel insights into our understanding of the host response to PEDV infection [ 14 ]. RSAD2, an important antiviral gene [ 46 ], has attracted extensive attention recently.…”

“…A few immune-related pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the NF-kappa B signaling pathway, and the PI3K/Akt/mTOR signaling pathway have been reported to play a role in responding to PEDV infection [ 14 ]. Importantly, the JAK-STAT signaling pathway regulates the adaptive and innate mechanisms related to mucosal immunity [ 15 ], and a previous study suggested that the JAK-STAT signaling pathway is activated after PEDV infection of host cells [ 16 ].…”

Genome-wide transcriptome analysis of porcine epidemic diarrhea virus virulent or avirulent strain-infected porcine small intestinal epithelial cells

“…The RNA-sequencing analysis of the PEDV-infected cultured pig intestinal cells revealed the perturbation of signal transducer and activator of transcription, cell cycle, and apoptosis pathways at the later stages of infection ( Shen et al., 2020 ). In a similar context, a few studies have identified several key host genes involved in regulating the antiviral immune response against PEDV such as FOSL1, IL1A, ISG15, and some other ISGs ( Hu et al., 2020 ; Sun et al., 2019 ; Wang et al., 2019 ). However, the host transcriptomic landscape at an early phase of PEDV infection and differences in the host response upon infection with an avirulent or a virulent PEDV strain are currently unknown.…”

Impacts of Epigenetic Processes on the Health and Productivity of Livestock

“…As summarized in Table 2 , epigenetic modifications have been identified as important regulatory mechanisms of milk production in dairy cows and other livestock species ( Singh et al, 2010 , 2011 ; Ibeagha-Awemu and Zhao, 2015 ). Significant differences of global DNA methylation levels in blood were reported between lactating dairy cows with high and low milk yield, indicating the association between milk yield and DNA methylation ( Dechow and Liu, 2018 ; Wang H. et al, 2019 ). Particularly, abnormal DNA methylation around the STAT5-binding enhancer in the αS1-casein promoter negatively regulated αS1-casein synthesis in milk during lactation, which could be affected by foreign stimulus, such as mastitis and daily milking times ( Platenburg et al, 1996 ; Vanselow et al, 2006 ; Nguyen et al, 2014 ).…”

“…E. coli -induced DNA methylation alteration in the form of DMCs in porcine mammary epithelial cells was mapped to the regulatory regions of immune-related genes, such as SDF4 , SRXN1 , CSF1 , and CXCL14 ( Sajjanar et al, 2019 ). A total of 1,885 H3K4me3 associated with 1,723 genes were identified in the jejunum of piglets with porcine epidemic diarrhea virus, revealing a positive correlation between higher H3K4me3 deposition and increased expression levels of some antiviral genes, including AS1 , OAS2 , EFNB2 , and CKS1B ( Wang H. et al, 2019 ). The overexpression of HDAC6 enhanced host resistance to porcine reproductive and respiratory syndrome virus (PRRSV) infection, resulting in repressed PRRSV production in vitro and lower viral load in the lung and less clinical symptoms in vivo ( Lu et al, 2017 ).…”