Identification of Riboflavin Metabolism Pathway in HepG2 Cells Expressing Genotype IV Swine Hepatitis E Virus ORF3 Protein.

IF 2.3 2区 农林科学 Q2 VETERINARY SCIENCES
Jing Tu, Shengping Wu, Lingjie Wang, Chi Meng, Gengxu Zhou, Jianhua Guo, Jixiang Li, Liting Cao, Zhenhui Song, Hanwei Jiao
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引用次数: 0

Abstract

(1) Background: Hepatitis E (HE) is a novel zoonotic disease caused by hepatitis E virus (HEV). In particular, swine hepatitis E virus (SHEV) genotype IV is one of the main genotypes that infect humans. Open reading frame 3 (ORF3) is an important virulence protein of SHEV, which is involved in virus assembly, release, and regulation of host cell signaling pathways. Circular RNAs (circRNAs), as a type of competitive endogenous RNA (ceRNA), have a closed-loop structure and are special non-coding RNA molecules. They participates in the regulation of multiple biological processes by adsorbing microRNAs (miRNAs). Riboflavin, also known as vitamin B2, is a component of the coenzyme of flavoenzymes in the body. When there is a deficiency of riboflavin, it will affect the biological oxidation process of the host, leading to metabolic disorders. In addition, riboflavin can also affect the synthesis, transportation and decomposition of lipids in the body. It mainly maintains the normal transportation process of fat in the liver. Therefore, the deficiency of riboflavin will lead to the disorder of lipid metabolism in the body. Thus, viral hepatitis is closely related to riboflavin metabolism. However, there are very few reports on SHEV ORF3 affecting the riboflavin metabolism of target cells and thereby influencing viral infection. Therefore, this study investigates this highly significant scientific issue. (2) Methods: In the previous research of our group, adenovirus was used to mediate the overexpression of SHEV ORF3 genotype IV in HepG2 cells. Total RNA was extracted for high-throughput sequencing of circRNAs and transcriptome. KEGG functional enrichment analysis was performed on the data to identify the differentially expressed circRNAs and miRNAs after SHEV infection, and the relevant circRNA-miRNA network in the riboflavin metabolism pathway in HepG2 cells was found. (3) Results: We identified 4 circRNAs in the riboflavin metabolism pathway of HepG2 cells expressing the ORF3 protein of SHEV genotype IV and successfully found 26 relevant circRNA-miRNA networks. (4) Conclusion: We successfully screened and identified circRNAs related to riboflavin metabolism, further identifying the circRNA-miRNA network and its functional targets. For the first time, we investigated the key mechanism by which ORF3 protein influences riboflavin metabolic pathways in target cells through circRNAs, preliminarily revealing that ariboflavinosis can lead to lipid metabolic disorder in the organism. This indicates a close association between viral HE and riboflavin metabolism.

表达基因IV型猪戊型肝炎病毒ORF3蛋白的HepG2细胞核黄素代谢途径的鉴定
(1)背景:戊型肝炎(HE)是由戊型肝炎病毒(HEV)引起的一种新型人畜共患疾病。特别是,猪戊型肝炎病毒(SHEV)基因型IV是感染人类的主要基因型之一。ORF3 (Open reading frame 3)是SHEV重要的毒力蛋白,参与病毒的组装、释放和宿主细胞信号通路的调控。环状RNA (Circular RNA, circRNAs)是一类竞争性内源性RNA (ceRNA),具有闭环结构,是一种特殊的非编码RNA分子。它们通过吸附microrna (miRNAs)参与多种生物过程的调控。核黄素,又称维生素B2,是人体内黄酮类酶辅酶的一种成分。当核黄素缺乏时,会影响宿主的生物氧化过程,导致代谢紊乱。此外,核黄素还能影响体内脂质的合成、运输和分解。它主要维持肝脏脂肪的正常运输过程。因此,核黄素缺乏会导致体内脂质代谢紊乱。因此,病毒性肝炎与核黄素代谢密切相关。然而,关于SHEV ORF3影响靶细胞核黄素代谢从而影响病毒感染的报道很少。因此,本研究探讨了这一高度重要的科学问题。(2)方法:本课组前期研究采用腺病毒介导hev ORF3基因型在HepG2细胞中的过表达。提取总RNA,对环状RNA和转录组进行高通量测序。对数据进行KEGG功能富集分析,鉴定SHEV感染后差异表达的circrna和mirna,发现HepG2细胞核黄素代谢通路中相关的circRNA-miRNA网络。(3)结果:我们在表达SHEV基因型ORF3蛋白的HepG2细胞的核黄素代谢途径中鉴定了4个circrna,并成功发现了26个相关的circRNA-miRNA网络。(4)结论:我们成功筛选并鉴定了与核黄素代谢相关的circrna,进一步鉴定了circRNA-miRNA网络及其功能靶点。我们首次研究了ORF3蛋白通过环状rna影响靶细胞核黄素代谢途径的关键机制,初步揭示了核黄素病可导致机体脂质代谢紊乱。这表明病毒HE与核黄素代谢密切相关。
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来源期刊
Veterinary Sciences
Veterinary Sciences VETERINARY SCIENCES-
CiteScore
2.90
自引率
8.30%
发文量
612
审稿时长
6 weeks
期刊介绍: Veterinary Sciences is an international and interdisciplinary scholarly open access journal. It publishes original that are relevant to any field of veterinary sciences, including prevention, diagnosis and treatment of disease, disorder and injury in animals. This journal covers almost all topics related to animal health and veterinary medicine. Research fields of interest include but are not limited to: anaesthesiology anatomy bacteriology biochemistry cardiology dentistry dermatology embryology endocrinology epidemiology genetics histology immunology microbiology molecular biology mycology neurobiology oncology ophthalmology parasitology pathology pharmacology physiology radiology surgery theriogenology toxicology virology.
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