Submit to Biomedicines Review for Biomedicines Propose a Special Issue

Journal Browser

Hepatitis B Virus Infection: From Cell Entry to Carcinogenesis. Understanding Viral Replication, Cell Pathogenesis, Disease and Treatments

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Microbiology in Human Health and Disease".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 7976

Share This Special Issue

Special Issue Editor

Dr. Rodrigo A. Villanueva

E-Mail Website
Guest Editor

Centro Ciencia & Vida, Fundación Ciencia & Vida, Avda. Zanartu 1482, Nunoa, Santiago 7780272, Chile
Interests: hepatitis B virus; viral replication; HBV X protein; HBx; protein posttranslational modification; viral chromatin regulation

Special Issue Information

Dear Colleagues,

Human hepatitis B virus (HBV) infection can progress to severe chronic diseases and hepatocellular carcinoma, which unfortunately are currently highly prevalent worldwide. While the availability of a prophylactic vaccine has reduced new cases over the decades, a therapeutic solution for chronic hepatitis B is still unavailable. On the other hand, important advances have been achieved on HBV virology. However, a comprehensive knowledge of some fundamental steps and factors involved in virus replication, persistence, and pathogenesis are still unreachable, and therefore, more research is required to accomplish strategies controlling HBV. To contribute new knowledge about this serious human pathogen, this Special Issue will bring together original research papers or review manuscripts on HBV infection with focus on viral replication and persistence, cell pathogenesis, hepatic disease, and anti-viral treatments.

Dr. Rodrigo A. Villanueva
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hepatitis B virus
entry
DNA genome replication
cccDNA chromatin regulation
particle assembly and egress
host factor interactions
HBx protein
viral persistence
cell pathogenesis
hepatic diseases
anti-viral treatments

Published Papers (3 papers)

Download All Papers

Research

Jump to: Review

8 pages, 817 KiB

Open AccessArticle

Chronic Hepatitis B Relapse Rates after Cessation of Tenofovir Alafenamide and Entecavir Therapy

by Chih-Wen Huang, Chen-Ta Yang, Pei-Yuan Su, Yang-Yuan Chen, Siou-Ping Huang and Hsu-Heng Yen

Biomedicines 2023, 11(3), 752; https://doi.org/10.3390/biomedicines11030752 - 1 Mar 2023

Cited by 2 | Viewed by 2274

Abstract

Chronic hepatitis B (CHB) relapse occurs after the cessation of nucleos(t)ide analogues (NUC) therapy due to the waning of viral suppression. Few studies have investigated the viral relapse rate and clinical relapse rate after tenofovir alafenamide (TAF) therapy. We compared the CHB relapse rate between TAF and entecavir therapy. We enrolled patients with chronic hepatitis B who underwent TAF or entecavir therapy. NUC therapy was terminated after HBeAg loss for 1 year in HBeAg-positive patients and after undetectable serum HBV DNA on three separate tests each >6 months apart in HBeAg-negative patients. After cessation of NUC therapy, we followed alanine aminotransferase (ALT) levels at 12, 24, and 48 weeks. Serum HBV DNA levels were checked if patients showed a two-fold elevation from the upper limit of normal ALT levels (41 IU/mL). Clinical relapse (CR) was defined as a two-fold elevation in ALT levels and HBV DNA levels > 2000 IU/mL. We then investigated the CR rate of HBV after cessation of TAF and entecavir therapy at 12, 24, and 48 weeks. Of the 117 patients enrolled, 78 were in the entecavir group and 39 were in the TAF group. At 12 weeks after cessation of NUC therapy, no patients had HBV CR in the entecavir group. However, three patients (CR cumulative rate 7.9%) had CR in the TAF group. At 24 weeks, the CR cumulative rate in the entecavir and TAF groups were 1.3% and 13.2%, respectively (p < 0.05). At 48 weeks, the CR cumulative rates were 9.2% and 24.2%, respectively (p = 0.055). Patients in the TAF group had a higher cumulative rate of CR than those in the entecavir group (log-rank p = 0.023). Furthermore, patients in the TAF group had earlier CR times than those in the entecavir group, especially in the first 24 weeks after cessation of therapies (p < 0.05). The cessation of TAF therapy had significantly earlier and higher CR rates than that of entecavir therapy. Close monitoring of liver function and HBV DNA levels may be necessary, especially within 24 weeks after cessation of TAF therapy. Full article

(This article belongs to the Special Issue Hepatitis B Virus Infection: From Cell Entry to Carcinogenesis. Understanding Viral Replication, Cell Pathogenesis, Disease and Treatments)

► Show Figures

Figure 1

Review

Jump to: Research

25 pages, 3026 KiB

Open AccessReview

Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions

by Rodrigo A. Villanueva and Alejandra Loyola

Biomedicines 2023, 11(6), 1674; https://doi.org/10.3390/biomedicines11061674 - 9 Jun 2023

Viewed by 1960

Abstract

Hepatitis B virus (HBV) is an enveloped DNA human virus belonging to the Hepadnaviridae family. Perhaps its main distinguishable characteristic is the replication of its genome through a reverse transcription process. The HBV circular genome encodes only four overlapping reading frames, encoding for the main canonical proteins named core, P, surface, and X (or HBx protein). However, pre- and post-transcriptional gene regulation diversifies the full HBV proteome into diverse isoform proteins. In line with this, hepatitis B virus X protein (HBx) is a viral multifunctional and regulatory protein of 16.5 kDa, whose canonical reading frame presents two phylogenetically conserved internal in-frame translational initiation codons, and which results as well in the expression of two divergent N-terminal smaller isoforms of 8.6 and 5.8 kDa, during translation. The canonical HBx, as well as the smaller isoform proteins, displays different roles during viral replication and subcellular localizations. In this article, we reviewed the different mechanisms of pre- and post-transcriptional regulation of protein expression that take place during viral replication. We also investigated all the past and recent evidence about HBV HBx gene regulation and its divergent N-terminal isoform proteins. Evidence has been collected for over 30 years. The accumulated evidence simply strengthens the concept of a new paradigm of the canonical HBx, and its smaller divergent N-terminal isoform proteins, not only during viral replication, but also throughout cell pathogenesis. Full article

(This article belongs to the Special Issue Hepatitis B Virus Infection: From Cell Entry to Carcinogenesis. Understanding Viral Replication, Cell Pathogenesis, Disease and Treatments)

► Show Figures

Figure 1

18 pages, 1329 KiB

Open AccessReview

Hepatitis B x (HBx) as a Component of a Functional Cure for Chronic Hepatitis B

by Mark A. Feitelson, Alla Arzumanyan, Ira Spector and Arvin Medhat

Biomedicines 2022, 10(9), 2210; https://doi.org/10.3390/biomedicines10092210 - 7 Sep 2022

Cited by 7 | Viewed by 3215

Abstract

Patients who are carriers of the hepatitis B virus (HBV) are at high risk of chronic liver disease (CLD) which proceeds from hepatitis, to fibrosis, cirrhosis and to hepatocellular carcinoma (HCC). The hepatitis B-encoded X antigen, HBx, promotes virus gene expression and replication, protects infected hepatocytes from immunological destruction, and promotes the development of CLD and HCC. For virus replication, HBx regulates covalently closed circular (ccc) HBV DNA transcription, while for CLD, HBx triggers cellular oxidative stress, in part, by triggering mitochondrial damage that stimulates innate immunity. Constitutive activation of NF-κB by HBx transcriptionally activates pro-inflammatory genes, resulting in hepatocellular destruction, regeneration, and increased integration of the HBx gene into the host genome. NF-κB is also hepatoprotective, which sustains the survival of infected cells. Multiple therapeutic approaches include direct-acting anti-viral compounds and immune-stimulating drugs, but functional cures were not achieved, in part, because none were yet devised to target HBx. In addition, many patients with cirrhosis or HCC have little or no virus replication, but continue to express HBx from integrated templates, suggesting that HBx contributes to the pathogenesis of CLD. Blocking HBx activity will, therefore, impact multiple aspects of the host–virus relationship that are relevant to achieving a functional cure. Full article

(This article belongs to the Special Issue Hepatitis B Virus Infection: From Cell Entry to Carcinogenesis. Understanding Viral Replication, Cell Pathogenesis, Disease and Treatments)

► Show Figures