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 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.
Highlights
Hepatitis B is an inflammatory disease of the liver caused by a partially double-stranded enveloped hepatitis B virus (HBV)
A number of the earlier nucleos(t)ide analogues (NAs), such as lamivudine, give rise to drug resistance Hepatitis B virus (HBV) strains, which can result in adverse long-term clinical effects
We review the various in vitro systems that have been used to study the molecular biology of the differentgenotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations
Summary
Hepatitis B is an inflammatory disease of the liver caused by a partially double-stranded enveloped hepatitis B virus (HBV). Approved HBV treatment regimens are restricted to interferon and nucleos(t)ide analogues (NAs), but these drugs can only efficiently suppress viral replication, without eliminating the virus [7,8,9]. HBV is classified into at least nine genotypes and 35 sub-genotypes, with distinct geographical distributions and prevalence [13,14,15] These (sub)genotypes can have different natural histories of infection, clinical manifestation, and response to antiviral agents [16]. It is important that the systems used to monitor antiviral efficacy of various agents are able to test the response of the various (sub)genotypes in order to ensure that the antiviral modalities are pan-genotypic (or customized if a pan-genotypic effect is not possible) and can be used in all regions of the world, especially where HBV is endemic, such as in Africa and Asia. We review the various in vitro systems that have been 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
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