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Current Opinion in Chemical Biology Jun 2019Hepatitis B virus (HBV) infections represent a significant burden on global public health. Current HBV treatments using nucleos(t)ide analogs (NAs) and PEG interferons... (Review)
Review
Hepatitis B virus (HBV) infections represent a significant burden on global public health. Current HBV treatments using nucleos(t)ide analogs (NAs) and PEG interferons cannot fully alleviate this burden as they do not affect the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Capsid assembly modulators (CAMs) disrupt the encapsidation of pre-genomic RNA and can cause nucleocapsid disassembly, thereby affecting multiple steps of HBV replication and reduction of cccDNA pools. This review provides a concise overview of the development of CAMs and the progress achieved in understanding their interactions with HBV core proteins.
Topics: Antiviral Agents; Capsid; Hepatitis B virus; Humans; Virus Assembly
PubMed: 30952041
DOI: 10.1016/j.cbpa.2019.02.009 -
World Journal of Gastroenterology May 2014Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the Hepadnaviridae family and is approximately 3.2 kb in length. Owing to a lack of proofreading... (Review)
Review
Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the Hepadnaviridae family and is approximately 3.2 kb in length. Owing to a lack of proofreading capacity during reverse transcription and a high replication rate, HBV exhibits as quasispecies. To detect the genetic mutations of HBV, many methods with different sensitivities and throughputs were developed. According to documentary records, HBV mutation and evolution were important vial parameters in predicting disease progression and therapeutic outcome. In this review, we separately discussed the correlation between HBV genomic mutations in four open reading frames and liver disease progression. Since some of the results were controversial from different laboratories, it remains to be seen whether functional analyses will confirm their role in modifying the course of infection.
Topics: Animals; Disease Progression; Genotype; Hepatitis B; Hepatitis B virus; Humans; Mutation; Open Reading Frames; Phenotype; Viral Proteins
PubMed: 24833874
DOI: 10.3748/wjg.v20.i18.5435 -
Cold Spring Harbor Perspectives in... Jan 2016The efficient replication of hepatitis B virus (HBV) requires the HBV regulatory hepatitis B virus X (HBx) protein. The exact contributions of HBx are not fully... (Review)
Review
The efficient replication of hepatitis B virus (HBV) requires the HBV regulatory hepatitis B virus X (HBx) protein. The exact contributions of HBx are not fully understood, in part because of the limitations of the assays used for its study. When HBV replication is driven from a plasmid DNA, the contribution of HBx is modest. However, there is an absolute requirement for HBx in assays that recapitulate the infectious virus life cycle. There is much evidence that HBx can contribute directly to HBV replication by acting on viral promoters embedded within protein coding sequences. In addition, HBx may also contribute indirectly by modulating cellular pathways to benefit virus replication. Understanding the mechanism(s) of HBx action during virus replication may provide insight into novel ways to disrupt chronic HBV replication.
Topics: DNA Replication; DNA, Viral; Gene Expression; Genome, Viral; Hepatitis B virus; Humans; Trans-Activators; Viral Regulatory and Accessory Proteins; Virus Replication
PubMed: 26747833
DOI: 10.1101/cshperspect.a021402 -
Trends in Genetics : TIG May 1989Infection with the hepatitis B virus (HBV) or related hepadnaviruses is associated with a wide spectrum of liver diseases, including hepatocellular carcinoma (HCC). In... (Review)
Review
Infection with the hepatitis B virus (HBV) or related hepadnaviruses is associated with a wide spectrum of liver diseases, including hepatocellular carcinoma (HCC). In this article we review the current state of knowledge about the structure, genetic organization and life cycle of HBV. The mechanisms of viral pathogenesis and HCC development remain poorly understood, but new approaches may soon begin to shed light on these areas.
Topics: Carcinoma, Hepatocellular; Genes, Viral; Hepatitis B; Hepatitis B virus; Liver Neoplasms
PubMed: 2547259
DOI: 10.1016/0168-9525(89)90057-7 -
Journal of the American Chemical Society May 2018For a three-dimensional structure to spontaneously self-assemble from many identical components, the steps on the pathway must be kinetically accessible. Many virus...
For a three-dimensional structure to spontaneously self-assemble from many identical components, the steps on the pathway must be kinetically accessible. Many virus capsids are icosahedral and assembled from hundreds of identical proteins, but how they navigate the assembly process is poorly understood. Capsid assembly is thought to involve stepwise addition of subunits to a growing capsid fragment. Coarse-grained models suggest that the reaction occurs on a downhill energy landscape, so intermediates are expected to be fleeting. In this work, charge detection mass spectrometry (CDMS) has been used to track assembly of the hepatitis B virus (HBV) capsid in real time. The icosahedral T = 4 capsid of HBV is assembled from 120 capsid protein dimers. Our results indicate that there are multiple pathways for assembly. Under conditions that favor a modest association energy there is no accumulation of large intermediates, which indicates that available pathways include ones on a downhill energy surface. Under higher salt conditions, where subunit interactions are strengthened, around half of the products of the initial assembly reaction have masses close to the T = 4 capsid and the other half are stalled intermediates which emerge abruptly at around 90 dimers, indicating a bifurcation in the ensemble of assembly paths. When incubated at room temperature, the 90-dimer intermediates accumulate dimers and gradually shift to higher mass and merge with the capsid peak. Though free subunits are present in solution, the stalled intermediates indicate the presence of a local minima on the energy landscape. Some intermediates may result from hole closure, where the growing capsid distorts to close the hole due to the missing capsid proteins or from a species where subsequent additions are particularly labile.
Topics: Capsid; Hepatitis B virus; Kinetics; Mass Spectrometry
PubMed: 29672035
DOI: 10.1021/jacs.8b01804 -
Viruses May 2022The recent review [...].
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Journal of Clinical Virology : the... May 2003The family of Hepadnaviridae is made up of members infecting birds (genus Avihepadnavirus) or mammals (genus Orthohepadnavirus). Hepatitis B virus (HBV), the...
BACKGROUND
The family of Hepadnaviridae is made up of members infecting birds (genus Avihepadnavirus) or mammals (genus Orthohepadnavirus). Hepatitis B virus (HBV), the hepadnavirus infecting humans, can be divided into the seven genotypes A-G. By definition, genotypes differ by more than 8% at the nucleotide level. However, some genotypes differ by more than 14% from others.
OBJECTIVES
The diversity of HBV genotypes necessitates great care in primer design to find primers suitable for routine diagnostic procedures that are highly conserved. Our aim was to find a target sequence on the HBV genome that is highly conserved among all known orthohepadnaviruses, to avoid false-negative polymerase chain reaction (PCR) results due to uncommon variants of HBV.
METHODS
Using an alignment of 177 genomes of orthohepadnaviruses from GenBank, we selected a primer pair from a highly conserved region, corresponding to hydrophobic transmembrane domains of the major surface protein of HBV.
RESULTS
The primer pair chosen was suitable to amplify genome sequences from HBV and to the genetically most distant woodchuck hepatitis virus in real-time PCR using the LightCycler, Roche. Moreover, the primers were suitable for accurate quantitation of both viral genomes over a range from 100 to 10(10) genomes/ml.
CONCLUSION
The described primers are useful for reliable detection and accurate quantitation of all known hepadnaviral genomes and may be used for the search for unknown orthohepadnaviruses.
Topics: Animals; DNA Primers; DNA, Viral; Genome, Viral; Hepatitis B Virus, Woodchuck; Hepatitis B virus; Humans; Orthohepadnavirus; Polymerase Chain Reaction
PubMed: 12727526
DOI: 10.1016/s1386-6532(02)00108-7 -
Nature Reviews. Microbiology Aug 2017
Topics: Hepatitis B virus; Nucleocapsid; RNA; Viral Core Proteins; Virus Assembly
PubMed: 28690322
DOI: 10.1038/nrmicro.2017.81 -
Emerging Infectious Diseases Apr 2013During an analysis of the virome of bats from Myanmar, a large number of reads were annotated to orthohepadnaviruses. We present the full genome sequence and a...
During an analysis of the virome of bats from Myanmar, a large number of reads were annotated to orthohepadnaviruses. We present the full genome sequence and a morphological analysis of an orthohepadnavirus circulating in bats. This virus is substantially different from currently known members of the genus Orthohepadnavirus and represents a new species.
Topics: Animals; Chiroptera; Genome, Viral; Hepatitis, Viral, Animal; Myanmar; Orthohepadnavirus; Phylogeny; Polymerase Chain Reaction; Prevalence; RNA, Viral; Sequence Analysis, DNA
PubMed: 23631923
DOI: 10.3201/eid1904.121655 -
Chinese Medical Journal Jan 2012To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis. (Review)
Review
OBJECTIVE
To review the development, mechanism, necessity and limitation of antiviral therapy in decompensated hepatitis B virus-related cirrhosis.
DATA SOURCES
Most information was pulled from a literature search (Pubmed 2000 to 2011) using the keywords of antiviral and decompensated hepatitis B virus-related cirrhosis. Relevant book chapters were also reviewed.
STUDY SELECTION
Well-controlled, prospective landmark studies and review articles on antiviral therapy in decompesated hepatitis B virus-related cirrhosis were selected.
RESULTS
Specific antiviral agents not only control viral replication, which permits liver transplantation, but also improve liver function so significantly that patients could be removed from the transplant waiting list. However, the emergence of drug-resistant mutants can result in treatment failure. Combination therapy is a save-strategy in drug-resistant.
CONCLUSIONS
Although the treatment of end-stage liver disease is still a challenge worldwide, antiviral therapy has altered the natural history of hepatitis B patients with decompensated cirrhosis. The approval of the new generation of antivirals is opening new perspectives for finding the optimal antiviral treatment for patients with decompensated cirrhosis and preventing antiviral resistance. A combination of antivirals may be one of the future strategies for fulfilling these goals.
Topics: Antiviral Agents; Hepatitis B virus; Humans; Liver Cirrhosis
PubMed: 22340574
DOI: No ID Found