The Natural Course of Chronic Hepatitis B Virus Infection and Its Management

Hadziyannis, Stephanos J.; Vassilopoulos, Dimitrios; Hadziyannis, Emilia

doi:10.1016/b978-0-12-405880-4.00007-x

Cited by 27 publications

(22 citation statements)

References 173 publications

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“…The stages are, first, an immune tolerance phase, then immune clearance of HBeAg as infected liver cells are attacked. Next comes a nonreplicative stage with low levels of HBV DNA and the presence of HBeAg antibodies; finally a reactivation phase may occur when core mutants arise that prevent HBeAg production while allowing HBV replication [6]. Although these four stages of chronic hepatitis B are usually linear in their progression, individuals may move forward or backward on this scale.…”

mentioning

confidence: 99%

Unveiling the Roles of HBV Polymerase for New Antiviral Strategies

Clark

2015

Future Virol.

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Infection with HBV is common worldwide, with over 350 million chronic carriers. Chronic HBV infection is associated with cirrhosis and hepatocellular carcinoma. All currently available oral antivirals are directed against the HBV polymerase enzyme, a reverse transcriptase. HBV polymerase contains several important domains and motifs which define its functions and reveal ways to further target it. This enzyme executes many functions required for the HBV replication cycle, including viral RNA binding, RNA packaging, protein priming, template switching, DNA synthesis and RNA degradation. In addition, HBV polymerase must interact with host proteins for its functions. Future therapeutics may inhibit not only the DNA synthesis steps which are carried out by the reverse transcriptase domain (as all current antivirals do) but other domains, functions and interactions which are essential to the HBV replication cycle.

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confidence: 99%

Unveiling the Roles of HBV Polymerase for New Antiviral Strategies

Clark

2015

Future Virol.

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“…Despite several attempts to devise a combination therapy that is more effective than single-compound, all current indications for HBV treatment are for monotherapy (Hadziyannis et al, 2013; Zhu et al, 2009). This is likely due to the single mode of inhibition for the components in the combined therapy trials.…”

Section: Potential For Developing Novel Rt Inhibitors In Combinationmentioning

confidence: 99%

Hepatitis B virus reverse transcriptase – Target of current antiviral therapy and future drug development

Clark

2015

Antiviral Research

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Hepatitis B virus (HBV) infections rely on the proper functioning of the viral polymerase enzyme, a specialized reverse transcriptase (RT) with multiple activities. All currently approved antiviral drugs for the treatment of chronic hepatitis B virus, except for interferon, target the RT and belong to the same chemical class - they are all nucleoside analogs. Viral DNA synthesis is carried out by the RT enzyme in several different steps, each with distinct RT conformational requirements. In principle, each stage may be targeted by distinct antiviral drugs. In particular, the HBV RT has the unique ability to initiate viral DNA synthesis using itself as a protein primer in a novel protein priming reaction. In order to help identify RT inhibitors and study their mechanisms of action, a number of experimental systems have been developed, each varying in its ability to dissect the protein priming and the subsequent stages of viral DNA synthesis reaction at the molecular level. Two of the most effective drugs to date, entecavir and tenofovir, can inhibit both the protein priming and the subsequent DNA elongation stages of HBV DNA synthesis. Interestingly, clevudine, a thymidine analog, can inhibit both protein priming and DNA elongation in a non-competitive manner and without being incorporated into the viral DNA. Thus, a nucleoside RT inhibitor (NRTI) can functionally mimic a non-NRTI (NNRTI) in its inhibition of the HBV RT. Therefore, novel NRTIs as well as NNRTIs may be developed to inhibit the DNA synthesis activity of the HBV RT. Furthermore, additional activities of the RT that are also essential to HBV replication, including specific recognition of the viral RNA and its packaging into viral nucleocapsids, may be exploited for antiviral development. To achieve a more potent inhibition of viral replication and ultimately cure chronic HBV infection, the next generation of anti-HBV therapies will likely need to include NRTIs, NNRTIs, and other agents that target the viral RT as well as other viral and host factors in various combinations. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B."

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“…Hepatotropic viruses are globally distributed and cause both acute [e.g., hepatitis A virus (HAV) and hepatitis E virus (HEV)] and chronic (e.g., HBV and HCV) infection, leading to liver fibrosis, cirrhosis, hepatocellular carcinoma, and, ultimately, end-stage liver disease requiring liver transplantation (85–88). Although functional HAV, HBV, and, recently, HEV vaccines are available along with direct-acting antivirals targeting HBV or HCV, these pathogens remain prevalent in the human population.…”

Section: Hepatotropic Virus Infection In Models With Emergent Propertiesmentioning

confidence: 99%

New Methods in Tissue Engineering: Improved Models for Viral Infection

et al. 2014

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New insights in the study of virus and host biology in the context of viral infection are made possible by the development of model systems that faithfully recapitulate the in vivo viral life cycle. Standard tissue culture models lack critical emergent properties driven by cellular organization and in vivo–like function, whereas animal models suffer from limited susceptibility to relevant human viruses and make it difficult to perform detailed molecular manipulation and analysis. Tissue engineering techniques may enable virologists to create infection models that combine the facile manipulation and readouts of tissue culture with the virus-relevant complexity of animal models. Here, we review the state of the art in tissue engineering and describe how tissue engineering techniques may alleviate some common shortcomings of existing models of viral infection, with a particular emphasis on hepatotropic viruses. We then discuss possible future applications of tissue engineering to virology, including current challenges and potential solutions.

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The Natural Course of Chronic Hepatitis B Virus Infection and Its Management

Cited by 27 publications

References 173 publications

Unveiling the Roles of HBV Polymerase for New Antiviral Strategies

Unveiling the Roles of HBV Polymerase for New Antiviral Strategies

Hepatitis B virus reverse transcriptase – Target of current antiviral therapy and future drug development

New Methods in Tissue Engineering: Improved Models for Viral Infection

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