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Journal of Hepatology Jun 2018All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another...
BACKGROUND & AIMS
All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear.
METHODS
We analysed sera from 124 Brazilian monkeys collected during 2012-2016 for hepadnaviruses using molecular and serological tools, and conducted evolutionary analyses.
RESULTS
We identified a novel orthohepadnavirus species in capuchin monkeys (capuchin monkey hepatitis B virus [CMHBV]). We found CMHBV-specific antibodies in five animals and high CMHBV concentrations in one animal. Non-inflammatory, probably chronic infection was consistent with an intact preCore domain, low genetic variability, core deletions in deep sequencing, and no elevated liver enzymes. Cross-reactivity of antisera against surface antigens suggested antigenic relatedness of HBV, CMHBV, and WMHBV. Infection-determining CMHBV surface peptides bound to the human HBV receptor (human sodium taurocholate co-transporting polypeptide), but preferentially interacted with the capuchin monkey receptor homologue. CMHBV and WMHBV pseudotypes infected human hepatoma cells via the human sodium taurocholate co-transporting polypeptide, and were poorly neutralised by HBV vaccine-derived antibodies, suggesting that cross-species infections may be possible. Ancestral state reconstructions and sequence distance comparisons associated HBV with humans, whereas primate hepadnaviruses as a whole were projected to NHP ancestors. Co-phylogenetic analyses yielded evidence for co-speciation of hepadnaviruses and New World NHP. Bayesian hypothesis testing yielded strong support for an association of the HBV stem lineage with hominoid ancestors. Neither CMHBV nor WMHBV was likely the ancestor of the divergent human HBV genotypes F/H found in American natives.
CONCLUSIONS
Our data suggest ancestral co-speciation of hepadnaviruses and NHP, and an Old World origin of the divergent HBV genotypes F/H. The identification of a novel primate hepadnavirus offers new perspectives for urgently needed animal models of chronic hepatitis B.
LAY SUMMARY
The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.
Topics: Amino Acid Sequence; Animals; Bayes Theorem; Brazil; Cebus; Evolution, Molecular; Genetic Speciation; Genome, Viral; Hepatitis B; Hepatitis B Antigens; Hepatitis B virus; Host Microbial Interactions; Humans; Models, Genetic; Monkey Diseases; Organic Anion Transporters, Sodium-Dependent; Orthohepadnavirus; Phylogeny; Primates; Receptors, Virus; Symporters; Virus Internalization
PubMed: 29428874
DOI: 10.1016/j.jhep.2018.01.029 -
Intervirology 2014Sequence heterogeneity is a feature of hepatitis B virus (HBV), the prototype member of the family Hepadnaviridae. Based on an intergroup divergence of greater than 7.5%... (Review)
Review
Sequence heterogeneity is a feature of hepatitis B virus (HBV), the prototype member of the family Hepadnaviridae. Based on an intergroup divergence of greater than 7.5% across the complete genome, HBV has been classified phylogenetically into 9 genotypes, A-I, with a putative 10th genotype 'J', isolated from a single individual. With between approximately 4 and 8% intergroup nucleotide divergence across the complete genome and good bootstrap support, genotypes A-D, F, H, and I are classified further into subgenotypes. There is a broad and highly statistically significant correlation between serological subtypes and genotypes, and in some cases, serological subtypes can be used to differentiate subgenotypes. The genotypes, and certain subgenotypes, have distinct geographical distributions and are important in both the clinical manifestation of infection and response to antiviral therapy. HBV genotypes/subgenotypes and genetic variability of HBV are useful in epidemiological and transmission studies, tracing human migrations, and in predicting the risk for the development of severe liver disease and response to antiviral therapy. Moreover, knowledge of the genotype/subgenotype is important in implementing preventative strategies. Thus, it is crucial that new strains are correctly assigned to their respective genotype/subgenotype and consistent, unambiguous, and generally accepted nomenclature is utilized.
Topics: Base Sequence; DNA, Viral; Genetic Variation; Genome, Viral; Genotype; Geography; Hepatitis B virus; Humans; Phylogeny
PubMed: 25034481
DOI: 10.1159/000360947 -
Viruses May 2016The Hepadnaviridae family of small, enveloped DNA viruses are characterized by a strict host range and hepatocyte tropism. The prototype hepatitis B virus (HBV) is a... (Review)
Review
The Hepadnaviridae family of small, enveloped DNA viruses are characterized by a strict host range and hepatocyte tropism. The prototype hepatitis B virus (HBV) is a major human pathogen and constitutes a public health problem, especially in high-incidence areas. Reporter-expressing recombinant viruses are powerful tools in both studies of basic virology and development of antiviral therapeutics. In addition, the highly restricted tropism of HBV for human hepatocytes makes it an ideal tool for hepatocyte-targeting in vivo applications such as liver-specific gene delivery. However, compact genome organization and complex replication mechanisms of hepadnaviruses have made it difficult to engineer replication-competent recombinant viruses that express biologically-relevant cargo genes. This review analyzes difficulties associated with recombinant hepadnavirus vector development, summarizes and compares the progress made in this field both historically and recently, and discusses future perspectives regarding both vector design and application.
Topics: Genes, Reporter; Genetic Vectors; Hepatitis B virus; Humans; Staining and Labeling; Virology
PubMed: 27171106
DOI: 10.3390/v8050125 -
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 -
Viruses May 2024The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense... (Review)
Review
The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense and restrict viral replication by impeding multiple steps during its intracellular lifecycle. This review summarizes many of the well-described restriction factors, their mechanisms of restriction, and counteractive measures of HBV, with a special focus on viral transcription. We discuss some of the limitations and knowledge gaps about the restriction factors, highlighting how these factors may be harnessed to facilitate therapeutic strategies against HBV.
Topics: Hepatitis B virus; Virus Replication; Humans; Host-Pathogen Interactions; Hepatitis B; Hepatocytes; Animals
PubMed: 38793645
DOI: 10.3390/v16050764 -
International Journal of Infectious... Sep 2023
Topics: Humans; Hepatitis B virus; Mental Disorders
PubMed: 37507084
DOI: 10.1016/j.ijid.2023.07.028 -
World Journal of Gastroenterology Apr 2011Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main... (Review)
Review
Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors are implicated in the pathogenesis of OBI. However, published data reporting the infectivity of OBI by transfusion are limited. Several aspects including OBI transmission, infectivity and its relation to the development of chronic liver diseases and hepatocellular carcinoma have to be resolved. The aim of the present review is to highlight recent data on OBI with a focus on its virological diagnosis and clinical outcome.
Topics: Blood Donors; Chronic Disease; Hepatitis B; Hepatitis B virus; Humans; Liver Diseases; Organ Transplantation; Virus Replication
PubMed: 21528070
DOI: 10.3748/wjg.v17.i15.1927 -
ACS Infectious Diseases May 2019Hepatitis B virus (HBV) chronically infects >250 million people and kills nearly a million annually, and current antivirals cannot clear the infection or adequately... (Review)
Review
Hepatitis B virus (HBV) chronically infects >250 million people and kills nearly a million annually, and current antivirals cannot clear the infection or adequately suppress disease. The virus replicates by reverse transcription, and the dominant antiviral drugs are nucleos(t)ide analogs that target the viral reverse transcriptase. We are developing antivirals targeting the other essential viral enzymatic activity, the ribonuclease H (RNaseH). HBV RNaseH inhibitors with efficacies in the low micromolar to nanomolar range against viral replication in culture have been identified in the α-hydroxytropolone and hydroxyimide chemotypes. Here, we review the promise of RNaseH inhibitors, their current structure-activity relationships, and challenges to optimizing the inhibitors into leads for clinical assessment.
Topics: Antiviral Agents; Enzyme Inhibitors; Hepatitis B virus; Ribonuclease H; Structure-Activity Relationship; Virus Replication
PubMed: 29565562
DOI: 10.1021/acsinfecdis.8b00045 -
Journal of the Chinese Medical... Aug 2012Hepatitis B virus (HBV) reactivation induced by cytotoxic chemotherapy is an important issue in cancer patients. An elevated HBV viral load usually precedes hepatitis... (Review)
Review
Hepatitis B virus (HBV) reactivation induced by cytotoxic chemotherapy is an important issue in cancer patients. An elevated HBV viral load usually precedes hepatitis flare, and hepatic decompensation and eventual death is not infrequent once viral reactivation is initiated. Reverse seroconversion from hepatitis B surface antigen (HBsAg)-negative to HBsAg-positive would also occur in hepatitis B core antibody (anti-HBc)-positive patients. The risk of HBV reactivation can be attributed to patient viral status and the regimen of chemotherapeutic agents. Chemotherapeutic regimens that contain steroid and rituximab can increase the risk of viral reactivation in lymphoma patients. Consequently, routine HBV marker screening, including HBsAg and anti-HBc, is mandatory prior to chemotherapy for all cancer patients, and prophylactic antiviral treatment is highly recommended for HBsAg-positive cases. However, for patients who are anti-HBc-positive and HBsAg-negative, so-called resolved hepatitis B patients, regular HBV viral load survey during the course of chemotherapy is necessary to early detect HBV reactivation. Currently, the role of antiviral prophylaxis for resolved hepatitis B patients is still unsettled.
Topics: Antineoplastic Agents; Carrier State; Hepatitis B; Hepatitis B virus; Humans; Virus Activation
PubMed: 22901718
DOI: 10.1016/j.jcma.2012.06.006 -
Frontiers in Immunology 2023
Topics: Antiviral Agents; Hepatitis B virus; Interferon-alpha; Hepatocytes
PubMed: 36817476
DOI: 10.3389/fimmu.2023.1135649