Abstract

Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China. In liver injury, exosomes may impede the interaction with chromatin in the target cell and transmit inflammatory, apoptosis, or regeneration signals through RNAs. Therefore, we attempted to determine the potential functions of exosomal RNAs using bioinformatics technology. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Exosomes from the CHB and HBV-ACLF patients showed distinct upregulation and downregulation patterns of differentially expressed genes compared with those from the HC subjects. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analysis further confirmed different patterns of biological functions and signalling pathways in CHB and HBV-ACLF. Then we chose two upregulated RNAs both in CHB and HBV-ACLF for further qPCR validation. It confirmed the significantly different expression levels in CHB and HBV-ACLF compared with HC. Our findings indicate selective packaging of the RNA cargo into exosomes under different HBV attacks; these may represent potential targets for the diagnosis and treatment of HBV-caused liver injury.

Highlights

  • Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China

  • Exosomes can transfer various classes of RNAs, including messenger RNAs (mRNAs) encoding specific proteins and non-coding RNAs (ncRNAs) of different sizes, such as long noncoding RNAs (lncRNAs), miRNAs, and circRNAs. Both coding RNAs and ncRNAs may act as protein cargos in exosomes, which transport proteins from one cell to another, impede the interaction with chromatin in the target cells, and modify gene expression

  • We revealed different expression profiles of RNAs in serum www.nature.com/scientificreports exosomes from healthy individuals and chronic hepatitis B (CHB) and HBV-acute-on-chronic liver failure (ACLF) patients

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Summary

Introduction

Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Information on gene expression in serum exosomes of these patients could provide molecular clues about regulatory pathways and networks in different types of liver injury caused by HBV and help identify gene targets for diagnosis and therapy

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