Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virology. Nov 12, 2015; 4(4): 313-322
Published online Nov 12, 2015. doi: 10.5501/wjv.v4.i4.313
Hepatitis delta virus: A fascinating and neglected pathogen
Celso Cunha, João Paulo Tavanez, Severin Gudima
Celso Cunha, João Paulo Tavanez, Global Health and Tropical Medicine, Medical Microbiology Unit, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal
Severin Gudima, Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 67874, United States
Author contributions: Cunha C coordinated and designed the study, wrote and edited the manuscript; Tavanez JP wrote the manuscript; Gudima S designed the study, wrote and edited the manuscript.
Supported by NIH to Dr. Gudima, Nos. R01CA166213, R21AI097647, and R21AI099696.
Conflict-of-interest statement: The authors declare to have no conflicts of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Celso Cunha, Associate Professor, Global Health and Tropical Medicine, Medical Microbiology Unit, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Rua da Junqueira, 100, 1349-008 Lisboa, Portugal. ccunha@ihmt.unl.pt
Telephone: +351-21-3652620 Fax: +351-21-3632105
Received: July 4, 2015
Peer-review started: July 10, 2015
First decision: July 31, 2015
Revised: October 14, 2015
Accepted: October 23, 2015
Article in press: October 27, 2015
Published online: November 12, 2015
Processing time: 135 Days and 22.9 Hours
Abstract

Hepatitis delta virus (HDV) is the etiologic agent of the most severe form of virus hepatitis in humans. Sharing some structural and functional properties with plant viroids, the HDV RNA contains a single open reading frame coding for the only virus protein, the Delta antigen. A number of unique features, including ribozyme activity, RNA editing, rolling-circle RNA replication, and redirection for a RNA template of host DNA-dependent RNA polymerase II, make this small pathogen an excellent model to study virus-cell interactions and RNA biology. Treatment options for chronic hepatitis Delta are scarce and ineffective. The disease burden is perhaps largely underestimated making the search for new, specific drugs, targets, and treatment strategies an important public health challenge. In this review we address the main features of virus structure, replication, and interaction with the host. Virus pathogenicity and current treatment options are discussed in the light of recent developments.

Keywords: Hepatitis delta virus; Hepatitis B virus; RNA replication; Pathogenesis; Treatment

Core tip: Hepatitis delta virus (HDV) is the etiologic agent of probably the most severe form of virus hepatitis. HDV replication and spread depends on the presence of hepatitis B virus which provides the envelope proteins coded exclusively by its own genome. About 20 million people are currently chronically infected with HDV and no specific therapy is still available. Here, we review the current knowledge on HDV biology, epidemiology, pathogenesis, and treatment. Future trends and perspectives are discussed in the light of recent developments on HDV biology and its interaction with the host.