Special Issue "Hepatitis B Virus: From Diagnostics to Treatments"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 30 June 2020.

Special Issue Editors

Dr. Mark W. Douglas
Website
Guest Editor
The University of Sydney, Sydney, Australia
Interests: Viral Hepatitis; Hepatitis B; Hepatitis C; Hepatitis D
Dr. Thomas Tu
Website
Guest Editor
The University of Sydney, Sydney, Australia
Interests: Hepatitis B Virus; Chronic Viral Hepatitis, Liver Cancer; Clonal Expansion; Virus Persistence; cccDNA; Integrated HBV DNA

Special Issue Information

Dear Colleagues,

Following the recent treatment revolution for Hepatitis C, there is now renewed international interest in Hepatitis B. The World Health Organization has set global elimination targets for Hepatitis B, and there is increased optimism for finding a Hepatitis B cure. In light of this interest, the respected international journal Viruses has decided to release a Special Issue on Hepatitis B, to update readers on the latest developments in this rapidly advancing field.

The Special Issue, titled “Hepatitis B Virus: From Diagnostics to Treatments”, will include a range of invited articles from leaders in the field. Articles will cover basic viral pathogenesis, viral immunology, natural history, epidemiology, and clinical aspects of Hepatitis B virus infection. The Special Issue will provide an overview of the history of Hepatitis B research, with a particular focus on recent advances in diagnostics and treatment.

Fifty years since the discovery of the Australia antigen, it is an exciting time for Hepatitis B virus research. This Special Issue aims to build that momentum, by updating Hepatitis B researchers, attracting new ones, and increasing general awareness of this devastating disease. Only continued international collaboration can achieve the ultimate aims: improving the lives of people with hepatitis B and global elimination of this virus as a public health threat.

Dr. Mark W. Douglas
Dr. Thomas Tu
Guest Editors

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 papers will be 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. Viruses 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 2000 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
  • Hepatitis B
  • chronic liver disease
  • hepatocellular carcinoma
  • liver cancer
  • chronic hepatitis
  • antiviral therapy

Published Papers (7 papers)

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Research

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Open AccessArticle
Hepatitis B Virus-X Downregulates Expression of Selenium Binding Protein 1
Viruses 2020, 12(5), 565; https://doi.org/10.3390/v12050565 - 20 May 2020
Abstract
Selenium binding protein 1 (SELENBP1) has been known to be reduced in various types cancer, and epigenetic change is shown to be likely to account for the reduction of SELNEBP1 expression. With cDNA microarray comparative analysis, we found that SELENBP1 is markedly decreased [...] Read more.
Selenium binding protein 1 (SELENBP1) has been known to be reduced in various types cancer, and epigenetic change is shown to be likely to account for the reduction of SELNEBP1 expression. With cDNA microarray comparative analysis, we found that SELENBP1 is markedly decreased in hepatitis B virus-X (HBx)-expressing cells. To clarify the effect of HBx on SELENBP1 expression, we compared the expression levels of SELENBP1 mRNA and protein by semi-quantitative RT-PCR, Northern blot, and Western blot. As expected, SELENBP1 expression was shown to be reduced in cells expressing HBx, and reporter gene analysis showed that the SELENBP1 promoter is repressed by HBx. In addition, the stepwise deletion of 5′ flanking promoter sequences resulted in a gradual decrease in basal promoter activity and inhibition of SELENBP1 expression by HBx. Moreover, immunohistochemistry on tissue microarrays containing 60 pairs of human liver tissue showed decreased intensity of SELENBP1 in tumor tissues as compared with their matched non-tumor liver tissues. Taken together, our findings suggest that inhibition of SELENBP1 expression by HBx might act as one of the causes in the development of hepatocellular carcinoma caused by HBV infection. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Open AccessArticle
Barriers to Hepatitis B Screening and Prevention for African Immigrant Populations in the United States: A Qualitative Study
Viruses 2020, 12(3), 305; https://doi.org/10.3390/v12030305 - 11 Mar 2020
Cited by 1
Abstract
Chronic hepatitis B infection (HBV) disproportionately affects African Immigrant (AI) communities in the U.S., with a reported infection rate of 15%. HBV screening rates within these communities are low. This study sought to better understand the socio-cultural determinants associated with low HBV screening [...] Read more.
Chronic hepatitis B infection (HBV) disproportionately affects African Immigrant (AI) communities in the U.S., with a reported infection rate of 15%. HBV screening rates within these communities are low. This study sought to better understand the socio-cultural determinants associated with low HBV screening among AI communities and identify potential strategies to help inform the development of effective HBV education and screening interventions. Seventeen in-depth interviews were conducted with community health experts working in AI communities throughout the U.S. Interviews explored the potential impact of culture, perception of health, awareness of HBV, religious practices, current screening practice, provider relationship, and behaviors towards general prevention. Interview data were analyzed using thematic analysis. Religious preferences and cultural norms affect health care access, perceptions towards prevention, awareness of HBV, and contribute to myths and stigma within this population. Participants reported a lack of HBV knowledge and awareness and barriers to health care access including, cost, language, racism, understanding of Western Medicine, and usage of traditional medicine. This study elucidates the role of religious and cultural beliefs as barriers to HBV screening and care. Results can contribute to public health efforts to increase awareness, screening and vaccination efforts within AI communities. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Review

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Open AccessReview
Molecular, Evolutionary, and Structural Analysis of the Terminal Protein Domain of Hepatitis B Virus Polymerase, a Potential Drug Target
Viruses 2020, 12(5), 570; https://doi.org/10.3390/v12050570 - 22 May 2020
Abstract
Approximately 250 million people are living with chronic hepatitis B virus (HBV) infections, which claim nearly a million lives annually. The target of all current HBV drug therapies (except interferon) is the viral polymerase; specifically, the reverse transcriptase domain. Although no high-resolution structure [...] Read more.
Approximately 250 million people are living with chronic hepatitis B virus (HBV) infections, which claim nearly a million lives annually. The target of all current HBV drug therapies (except interferon) is the viral polymerase; specifically, the reverse transcriptase domain. Although no high-resolution structure exists for the HBV polymerase, several recent advances have helped to map its functions to specific domains. The terminal protein (TP) domain, unique to hepadnaviruses such as HBV, has been implicated in the binding and packaging of the viral RNA, as well as the initial priming of and downstream synthesis of viral DNA—all of which make the TP domain an attractive novel drug target. This review encompasses three types of analysis: sequence conservation analysis, secondary structure prediction, and the results from mutational studies. It is concluded that the TP domain of HBV polymerase is comprised of seven subdomains (three unstructured loops and four helical regions) and that all three loop subdomains and Helix 5 are the major determinants of HBV function within the TP domain. Further studies, such as modeling inhibitors of these critical TP subdomains, will advance the TP domain of HBV polymerase as a therapeutic drug target in the progression towards a cure. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Open AccessReview
The Lived Experience of Chronic Hepatitis B: A Broader View of Its Impacts and Why We Need a Cure
Viruses 2020, 12(5), 515; https://doi.org/10.3390/v12050515 - 07 May 2020
Abstract
Chronic hepatitis B (CHB) is one of the most widespread liver diseases in the world. It is currently incurable and can lead to liver cirrhosis and cancer. The considerable impacts on society caused by CHB through patient mortality, morbidity, and economic loss are [...] Read more.
Chronic hepatitis B (CHB) is one of the most widespread liver diseases in the world. It is currently incurable and can lead to liver cirrhosis and cancer. The considerable impacts on society caused by CHB through patient mortality, morbidity, and economic loss are well-recognised in the field. This is, however, a narrow view of the harms, given that people living with CHB can be asymptomatic for the majority of their life-long infection. Of less-appreciated importance are the psychosocial harms, which can continue throughout an affected person’s lifetime. Here we review the broad range of these impacts, which include fear and anxiety; financial loss and instability; stigma and discrimination; and rejection by society. Importantly, these directly affect patient diagnosis, management, and treatment. Further, we highlight the roles that the research community can play in taking these factors into account and mitigating them. In particular, the development of a cure for hepatitis B virus infection would alleviate many of the psychosocial impacts of CHB. We conclude that there should be a greater recognition of the full impacts associated with CHB to bring meaningful, effective, and deliverable results to the global community living with hepatitis B. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Open AccessReview
In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations
Viruses 2020, 12(3), 353; https://doi.org/10.3390/v12030353 - 23 Mar 2020
Abstract
Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range [...] Read more.
Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Open AccessReview
Impact of the Interaction of Hepatitis B Virus with Mitochondria and Associated Proteins
Viruses 2020, 12(2), 175; https://doi.org/10.3390/v12020175 - 04 Feb 2020
Cited by 1
Abstract
Around 350 million people are living with hepatitis B virus (HBV), which can lead to death due to liver cirrhosis and hepatocellular carcinoma (HCC). Various antiviral drugs/nucleot(s)ide analogues are currently used to reduce or arrest the replication of this virus. However, many studies [...] Read more.
Around 350 million people are living with hepatitis B virus (HBV), which can lead to death due to liver cirrhosis and hepatocellular carcinoma (HCC). Various antiviral drugs/nucleot(s)ide analogues are currently used to reduce or arrest the replication of this virus. However, many studies have reported that nucleot(s)ide analogue-resistant HBV is circulating. Cellular signaling pathways could be one of the targets against the viral replication. Several studies reported that viral proteins interacted with mitochondrial proteins and localized in the mitochondria, the powerhouse of the cell. And a recent study showed that mitochondrial turnover induced by thyroid hormones protected hepatocytes from hepatocarcinogenesis mediated by HBV. Strong downregulation of numerous cellular signaling pathways has also been reported to be accompanied by profound mitochondrial alteration, as confirmed by transcriptome profiling of HBV-specific CD8 T cells from chronic and acute HBV patients. In this review, we summarize the ongoing research into mitochondrial proteins and/or signaling involved with HBV proteins, which will continue to provide insight into the relationship between mitochondria and HBV and ultimately lead to advances in viral pathobiology and mitochondria-targeted antiviral therapy. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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Open AccessReview
Host Transcription Factors in Hepatitis B Virus RNA Synthesis
Viruses 2020, 12(2), 160; https://doi.org/10.3390/v12020160 - 30 Jan 2020
Cited by 1
Abstract
The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently closed circular DNA [...] Read more.
The hepatitis B virus (HBV) chronically infects over 250 million people worldwide and is one of the leading causes of liver cancer and hepatocellular carcinoma. HBV persistence is due in part to the highly stable HBV minichromosome or HBV covalently closed circular DNA (cccDNA) that resides in the nucleus. As HBV replication requires the help of host transcription factors to replicate, focusing on host protein–HBV genome interactions may reveal insights into new drug targets against cccDNA. The structural details on such complexes, however, remain poorly defined. In this review, the current literature regarding host transcription factors’ interactions with HBV cccDNA is discussed. Full article
(This article belongs to the Special Issue Hepatitis B Virus: From Diagnostics to Treatments)
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