Pathogenesis of Viral Hepatitis-Induced Chronic Liver Disease: Role of Extracellular Vesicles

Hong Kiat Lim,Carolina Soekmadji,Grant A Ramm,Gary P Jeffrey

doi:10.3389/fcimb.2020.587628

Abstract

Extracellular vesicles are encapsulated lipid nanoparticles secreted by a variety of cell types in living organisms. They are known to carry proteins, metabolites, nucleic acids, and lipids as their cargoes and are important mediators of intercellular communication. The role of extracellular vesicles in chronic liver disease has been reported. Chronic liver disease such as viral hepatitis accounts for a significant mortality and morbidity burden worldwide. Hepatic fibrosis has been commonly associated with the chronic form of viral hepatitis, which results in end-stage liver disease, including cirrhosis, liver failure, and carcinoma in some patients. In this review, we discuss the potential role of extracellular vesicles in mediating communication between infectious agents (hepatitis B and C viruses) and host cells, and how these complex cell-cell interactions may facilitate the development of chronic liver disease. We will further discuss how understanding their biological mechanism of action might be beneficial for developing therapeutic strategies to treat chronic liver disease.

Highlights

Extracellular vesicles (EV), first described over four decades ago (Chargaff and West, 1946; Wolf, 1967), have gained recognition as an important mediator of intercellular communication in chronic liver disease (CLD) (Ramakrishnaiah et al, 2013; Hirsova et al, 2016; Devhare et al, 2017; Banales et al, 2019)
This study demonstrated the resistance of EVs to antibody neutralization, suggesting the possibility for EVs to act as a physical barrier between the infectious viral particles and the immune system, allowing viruses to establish persistence in chronic patients (Sanada et al, 2016)
The Role of Extracellular Vesicles as a Biomarker for Virus-Associated Chronic Liver Disease EVs from blood and urine may be used as a potential noninvasive diagnostic tool for early detection of viral-associated CLD and hepatocellular carcinoma (HCC), which remain challenging to diagnose in part because most patients remain asymptomatic in early stages of disease pathogenesis

Summary

Introduction

Extracellular vesicles (EV), first described over four decades ago (Chargaff and West, 1946; Wolf, 1967), have gained recognition as an important mediator of intercellular communication in chronic liver disease (CLD) (Ramakrishnaiah et al, 2013; Hirsova et al, 2016; Devhare et al, 2017; Banales et al, 2019). Studies in human immunodeficiency virus (HIV) have demonstrated the presence of viral transactivating response (TAR) element RNA in EVs isolated by gel filtration Sephadex G-10 spin column and Nanotrap particle A for CD63+ vesicles from sera of HIV-1 infected patients and supernatants of cultured infected J1.1 cells respectively (Table 1) (Narayanan et al, 2013; Sampey et al, 2016).

Results

Conclusion