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Article

Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus

1
The College of Veterinary Medicine, Southwest University, Chongqing 402460, China
2
Ministry of Agriculture and Rural Affairs Key Laboratory of Crop Genetic Resources and Germplasm Innovation in Karst Region, Institute of Animal Husbandry and Veterinary Medicine of Guizhou Academy of Agricultural Science, Guiyang 550005, China
3
Center for Translational Cancer Research, Brown Foundation Institute of Molecular Medicine, 1825 Pressler St., Suite 310, Houston, TX 77030, USA
4
Hainan Key Laboratory of Tropical Animal Reproduction & Breeding and Epidemic Disease Research, School of Tropical Agriculture and Forestry, Hainan University, Haikou 570228, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Microorganisms 2025, 13(12), 2654; https://doi.org/10.3390/microorganisms13122654 (registering DOI)
Submission received: 28 October 2025 / Revised: 19 November 2025 / Accepted: 20 November 2025 / Published: 22 November 2025
(This article belongs to the Section Virology)

Abstract

The open reading frame 3 (ORF3) protein of the swine hepatitis E virus (SHEV) is a critical virulence factor implicated in viral infection, yet its precise mechanisms remain poorly understood. Circular RNAs (circRNAs) have emerged as key regulators of gene expression during viral infections by functioning as miRNA sponges. This study aimed to identify key circRNAs and construct a potential circRNA-miRNA-mRNA regulatory network associated with the viral infection pathway in HepG2 cells expressing genotype IV SHEV ORF3. Based on our previous high-throughput circRNA and transcriptome sequencing data from HepG2 cells with adenovirus-mediated ORF3 overexpression, we screened for differentially expressed circRNAs and mRNAs linked to viral infection pathways. Using bioinformatic tools, we predicted miRNAs targeted by these mRNAs and those that could bind to the circRNAs, ultimately constructing a competing endogenous RNA (ceRNA) network with Cytoscape. We identified 31 differentially expressed circRNAs and 7 mRNAs (HSPA8, HSPA1B, EGR2, CXCR4, SOCS3, NOTCH3, and ZNF527) related to viral infection. A potential ceRNA network comprising 32 circRNAs, 23 miRNAs, and the 7 mRNAs was constructed. Core circRNAs, including ciRNA203, circRNA14936, and circRNA5562, may act as miRNA sponges to regulate the expression of these mRNAs. This network suggests a novel mechanism by which SHEV ORF3 might modulate host cell functions to facilitate viral infection.
Keywords: SHE; SHEV ORF3; HepG2; viral infection; circRNA-miRNA-mRNA network SHE; SHEV ORF3; HepG2; viral infection; circRNA-miRNA-mRNA network

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MDPI and ACS Style

Jiao, H.; Wang, L.; Meng, C.; Wu, S.; Qi, Y.; Guo, J.; Li, J.; Cao, L.; Zhao, Y.; Wen, J.J.; et al. Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus. Microorganisms 2025, 13, 2654. https://doi.org/10.3390/microorganisms13122654

AMA Style

Jiao H, Wang L, Meng C, Wu S, Qi Y, Guo J, Li J, Cao L, Zhao Y, Wen JJ, et al. Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus. Microorganisms. 2025; 13(12):2654. https://doi.org/10.3390/microorganisms13122654

Chicago/Turabian Style

Jiao, Hanwei, Lingjie Wang, Chi Meng, Shengping Wu, Yubo Qi, Jianhua Guo, Jixiang Li, Liting Cao, Yu Zhao, Jake J. Wen, and et al. 2025. "Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus" Microorganisms 13, no. 12: 2654. https://doi.org/10.3390/microorganisms13122654

APA Style

Jiao, H., Wang, L., Meng, C., Wu, S., Qi, Y., Guo, J., Li, J., Cao, L., Zhao, Y., Wen, J. J., & Wang, F. (2025). Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus. Microorganisms, 13(12), 2654. https://doi.org/10.3390/microorganisms13122654

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