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Journal of Clinical Virology : the... May 2006
Review
Topics: Hepatitis B; Hepatitis B virus; Nucleic Acid Amplification Techniques; Transfusion Reaction
PubMed: 16831686
DOI: 10.1016/s1386-6532(06)80001-6 -
Journal of Medical Virology Jul 2002Hepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and... (Review)
Review
Hepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is the result of complicated viral-host interactions. As in other infections with non-cythopatic viruses, the immune response is thought to play a crucial role in disease pathogenesis but there is increasing evidence that a variety of viral mechanisms, some depending on the function of virally encoded proteins, have a profound impact on the infected hepatocytes, the liver microenvironment, and host anti-viral responses. Indeed, the virus has evolved multiple mechanisms to ensure its success in infecting a susceptible host. The essential aspects of the life cycle of HBV and the host immune response are reviewed and recent new developments in the molecular virology of HBV, including experimental animal models, in the role of accessory viral proteins in disease pathogenesis and HCC development and in the characterisation of the T cell response in the control of HBV infection, are highlighted.
Topics: Animals; Disease Models, Animal; Hepatitis B; Hepatitis B virus; Humans; Mice
PubMed: 12116045
DOI: 10.1002/jmv.10096 -
Clinics in Liver Disease May 2004Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is... (Review)
Review
Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1).
Topics: DNA, Viral; Genome, Viral; Hepatitis B; Hepatitis B virus; Humans; Open Reading Frames; Viral Load; Virus Replication
PubMed: 15481342
DOI: 10.1016/j.cld.2004.02.009 -
Journal of Clinical Virology : the... Dec 2005The treatment of HBV infected patients with analogues of nucleos(t)ides, including lamivudine and adefovir dipivoxil, has significantly increased the rate of anti-HBe... (Review)
Review
The treatment of HBV infected patients with analogues of nucleos(t)ides, including lamivudine and adefovir dipivoxil, has significantly increased the rate of anti-HBe seroconversion and therefore reduced the impact of chronic hepatitis B (CHB) on liver disease. Altogether, these antivirals have offered novel options for the treatment of patients who did not respond to previous therapy with interferon alpha, the only available treatment against CHB until 1998. However, therapies using analogues of nucleos(t)ides have been confronted with viral resistances which are often associated to with worsening of liver disease. Drug resistance is conferred by the appearance of one or several mutations within the HBV polymerase gene. These mutations confer to the mutant viral population a phenotypic advantage over the wild-type pretherapeutic viral quasispecies, as they induce a reduction of drug susceptibility of mutant strains in vivo. This reduction of drug susceptibility can be as well measured in vitro, i.e in cell culture, using phenotypic assays. The detection of these mutations has become of crucial importance to better adapt clinical option to the virological status of the patient. Genotypic and more recently phenotypic assays have been developed and both assays can be used for drug resistance testing. Genotypic assay gives information about already characterized mutations associated with viral resistance, while phenotypic testing measures the overall drug susceptibility of patient-derived viral strains in cell culture. These assays are described and their potential use in the clinical setting is discussed.
Topics: Drug Resistance, Viral; Genotype; Hepatitis B; Hepatitis B virus; Humans; Phenotype; Reverse Transcriptase Inhibitors
PubMed: 16461221
DOI: 10.1016/s1386-6532(05)80008-3 -
Infection, Genetics and Evolution :... Oct 2017The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted...
The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the latter, it is known that recombination played a major role in the emergence and genetic diversification of novel genotypes. In this regard, the quantification of viral recombination in each genotype can provide relevant information to devise expectations about the evolutionary trends of the epidemic. Here we measured the amount of this evolutionary force by estimating global and local recombination rates in >4700 HBV complete genome sequences corresponding to nine (A to I) HBV genotypes. Counterintuitively, we found that genotype E presents extremely high levels of recombination, followed by genotypes B and C. On the other hand, genotype G presents the lowest level, where recombination is almost negligible. We discuss these findings in the light of known characteristics of these genotypes. Additionally, we present a phylogenetic network to depict the evolutionary history of the studied HBV genotypes. This network clearly classified all genotypes into specific groups and indicated that diverse pairs of genotypes are derived from a common ancestor (i.e., C-I, D-E and, F-H) although still the origin of this virus presented large uncertainty. Altogether we conclude that the amount of observed recombination is heterogeneous among HBV genotypes and that this heterogeneity can influence on the future expansion of the epidemic.
Topics: Base Composition; Evolution, Molecular; Genome, Viral; Genotype; Hepatitis B virus; Phylogeny; Recombination, Genetic; Sequence Analysis, DNA
PubMed: 28827173
DOI: 10.1016/j.meegid.2017.08.015 -
Virology Journal Mar 2011In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the... (Review)
Review
In Pakistan, there are estimated 7-9 million carriers of hepatitis B virus (HBV) with a carrier rate of 3-5%. This article reviews the available literature about the prevalence, risk factors, awareness status and genotypes of the HBV in Pakistan by using key words; HBV prevalence, risk factors, awareness status and genotypes in Pakistani population in PubMed, PakMediNet, Directory of Open Access Journals (DOAJ) and Google Scholar. One hundred and six different studies published from 1998 to 2010 were included in this study. Weighted mean and standard deviation were determined for each population group. The percentage of hepatitis B virus infection in general population was 4.3318% ± 1.644%, healthy blood donors (3.93% ± 1.58%), military recruits (4.276% ± 1.646%), healthcare persons (3.25% ± 1.202%), pregnant women (5.872% ± 4.984), prisoners (5.75% ± 0.212%), surgical patients (7.397% ± 2.012%), patients with cirrhosis (28.87% ± 11.90%), patients with HCC (22% ± 2.645%), patients with hepatitis (15.896% ± 14.824%), patients with liver diseases (27.54% ± 6.385%), multiple transfused patients (6.223% ± 2.121%), opthalmic patients (3.89% ± 1.004%) and users of injectable drugs (14.95% ± 10.536%). Genotype D (63.71%) is the most prevalent genotype in Pakistani population. Mass vaccination and awareness programs should be initiated on urgent basis especially in populations with HBV infection rates of more than 5%.
Topics: Awareness; Genotype; Hepatitis B; Hepatitis B virus; Humans; Pakistan; Prevalence; Risk Factors
PubMed: 21375760
DOI: 10.1186/1743-422X-8-102 -
Journal of Clinical Virology : the... Dec 2005In Latin America, despite the paucity of population studies, hepatitis B is considered endemic. The western Amazonia is a highly endemic area where hepatitis D is also... (Review)
Review
In Latin America, despite the paucity of population studies, hepatitis B is considered endemic. The western Amazonia is a highly endemic area where hepatitis D is also prevalent. In this area, outbreaks of fulminant hepatitis due to H13V and HDV are frequently reported. Non-safe sexual activity seems to be the most important transmission route, but intrafamilial transmission, during early childhood, is extremely significant in Amazonia. The H13V genotype distribution is heterogeneous with a high prevalence of genotype F in the Amazonian region and genotype A in all other areas. In the region where Asian and Italian immigration occurred, genotypes B, C and D are also described.
Topics: Hepatitis B; Hepatitis B virus; Humans; Latin America
PubMed: 16461213
DOI: 10.1016/s1386-6532(05)80022-8 -
Intervirology 2001In the middle 80s, recombinant hepatitis B virus cores (HBc) gave onset to icosahedral virus-like particles (VLPs) as a basic class of non-infectious carriers of foreign... (Review)
Review
In the middle 80s, recombinant hepatitis B virus cores (HBc) gave onset to icosahedral virus-like particles (VLPs) as a basic class of non-infectious carriers of foreign immunological epitopes. The recombinant HBc particles were used to display immunodominant epitopes of hepatitis B, C, and E virus, human rhinovirus, papillomavirus, hantavirus, and influenza virus, human and simian immunodeficiency virus, bovine and feline leukemia virus, foot-and-mouth disease virus, murine cytomegalovirus and poliovirus, and other virus proteins, as well as of some bacterial and protozoan protein epitopes. Practical applicability of the HBc particles as carriers was enabled by their ability to high level synthesis and correct self-assembly in heterologous expression systems. The interest in the HBc VLPs was reinforced by the resolution of their fine structure by electron cryomicroscopy and X-ray crystallography, which revealed an unusual alpha-helical organization of dimeric units of HBc shells, alternative packing into icosahedrons with T = 3 and T = 4 symmetry, and the existence of long protruding spikes. The tips of the latter seem to be the optimal targets for the display of foreign sequences up to 238 amino acid residues in length. Combination of numerous experimental data on epitope display with the precise structural information enables a knowledge-based design of diagnostic, and vaccine and gene therapy tools on the basis of the HBc particles.
Topics: Amino Acid Sequence; Animals; Antigens, Viral; Epitopes, B-Lymphocyte; Epitopes, T-Lymphocyte; Genetic Therapy; Hepatitis B virus; Humans; Models, Molecular; Molecular Conformation; Molecular Sequence Data; Vaccines, Synthetic; Viral Core Proteins; Viral Vaccines
PubMed: 11509871
DOI: 10.1159/000050037 -
Current Protocols in Nucleic Acid... Apr 2006The "unnatural" l-nucleoside beta-l-2'-deoxythymidine (L-dT) is a potent, specific, and selective inhibitor of the replication of hepatitis B virus (HBV), which is...
The "unnatural" l-nucleoside beta-l-2'-deoxythymidine (L-dT) is a potent, specific, and selective inhibitor of the replication of hepatitis B virus (HBV), which is currently in Phase III clinical trials. This unit describes, in detail, a semi-large-scale synthesis of l-dT. This convenient methodology produces l-dT in six steps starting with l-ribose and ending with a satisfactory overall yield of l-dT, and may be applied to other 2'-deoxynucleosides, incorporating different heterocyclic bases.
Topics: Antiviral Agents; Hepatitis B virus; Thymidine; Virus Replication
PubMed: 18428950
DOI: 10.1002/0471142700.nc1403s24 -
Virus Research Jan 2020Hepatitis B virus (HBV) is the prototype of hepadnaviruses, which can be subgrouped into orthohepadnaviruses infecting mammals, avihehepadnaviruses of birds,... (Review)
Review
Hepatitis B virus (HBV) is the prototype of hepadnaviruses, which can be subgrouped into orthohepadnaviruses infecting mammals, avihehepadnaviruses of birds, metahepadnaviruses of fish, and herpetohepadnaviruses of amphibians and reptiles. The middle (M) envelope protein and e antigen are new additions in the evolution of hepadnaviruses. They are alternative translation products of the transcripts for small (S) envelope and core proteins, respectively. For HBV, e antigen is converted from precore/core protein by removal of N-terminal signal peptide followed by furin-mediated cleavage of the basic C-terminus. This study compared old and newly discovered hepadnaviruses for their envelope protein and e antigen expression or processing. The S protein of bat hepatitis B virus (BHBV) and two metahepadnaviruses is probably myristoylated, in addition to two avihepadnaviruses. While most orthohepadnaviruses express a functional M protein with N-linked glycosylation near the amino-terminus, most metahepadnaviruses and herpetohepadnaviruses probably do not. These viruses and one orthohepadnavirus, the shrew hepatitis B virus, lack an open precore region required for e antigen expression. Potential furin cleavage sites (RXXR sequence) can be found in e antigen precursors of orthohepadnaviruses and avihepadnaviruses. Despite much larger precore/core proteins of avihepadnaviruses and their limited sequence homology with those of orthohepadnaviruses, their proximal RXXR motif can be aligned with a distal RXXR motif for orthohepadnaviruses. Thus, furin or another basic endopeptidase is probably the shared enzyme for hepadnaviral e antigen maturation. A precore-derived cysteine residue is involved in forming intramolecular disulfide bond of HBV e antigen to prevent particle formation, and such a cysteine residue is conserved for both orthohepadnaviruses and avihepadnaviruses. All orthohepadnaviruses have an X gene, while all avihepadnaviruses can express the e antigen. M protein expression appears to be the most recent event in the evolution of hepadnaviruses.
Topics: Amino Acid Sequence; Antigens, Viral; Biological Evolution; Evolution, Molecular; Gene Expression Regulation, Viral; Genome, Viral; Genomics; Hepadnaviridae; Hepadnaviridae Infections; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Humans; Viral Envelope Proteins
PubMed: 31785305
DOI: 10.1016/j.virusres.2019.197825