Bioinformatics Analysis of the Key lncRNAs of the Viral Response Pathway in HepG2 Expressing Genotype IV Swine Hepatitis E Virus ORF3.

Hepatitis E virus (HEV) is one of the pathogens that cause viral hepatitis, and its clinical symptoms can manifest as acute, chronic viral hepatitis, or asymptomatic infection. Among them, swines are the main animal source of HEV. Open reading frame 3 (ORF3) is a multifunctional protein essential for swine hepatitis E virus (SHEV) infection and release, involved in biological processes such as intracellular signal transduction regulation. In our preliminary research, we utilized adenovirus-mediated overexpression of type IV SHEV ORF3 in HepG2 cells, extracted total RNA, and performed high-throughput long non coding RNAs (lncRNAs) and transcriptome sequencing. In this study, we screened and analyzed lncRNAs involved in the GO pathway: viral process (GO: 0016032), and combined them with differentially expressed mRNAs for target gene prediction. We identified two lncRNAs-lncRNA AL137002 (MSTRG. 7478) and lncRNA AL049840 (MSTRG. 8427)-that are associated with viral progression and have p ≤ 0.05 in HepG2 cells expressing ORF3 of porcine hepatitis E virus type IV. We predicted their five lncRNA-mRNA networks, which are lncRNA AL137002 (MSTRG. 7478)-ENST0000375440, lncRNA AL137002 (MSTRG. 7478)-ENST0000375441, lncRNA AL049840(MSTRG. 8427)-ENST0000246489, lncRNA AL049840 (MSTRG. 8427)-ENST0000554280 and lncRNA AL049840 (MSTRG. 8427)-ENST0000452929, and were used to predict their lncRNA mRNA binding sites and construct relevant molecular models. This will lay a solid foundation for further revealing the function of SHEV ORF3 and elucidating the mechanism of SHEV infection.