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Virology May 2019Limited sampling means that relatively little is known about the diversity and evolutionary history of mammalian members of the Hepadnaviridae (genus Orthohepadnavirus)....
Limited sampling means that relatively little is known about the diversity and evolutionary history of mammalian members of the Hepadnaviridae (genus Orthohepadnavirus). An important case in point are shrews, the fourth largest group of mammals, but for which there is limited knowledge on the role they play in viral evolution and emergence. Here, we report the discovery of a novel shrew hepadnavirus. The newly discovered virus, denoted shrew hepatitis B virus (SHBV), is divergent to be considered a new species of Orthohepadnavirus. Phylogenetic analysis revealed that these viruses were usually most closely related to TBHBV (tent-making bat hepatitis B virus), known to be able to infect human hepatocytes, and had a similar genome structure, although SHBV fell in a more basal position in the surface protein phylogeny. In sum, these data suggest that shrews are natural hosts for hepadnaviruses and may have played an important role in their long-term evolution.
Topics: Amino Acid Sequence; Animals; China; Evolution, Molecular; Genome, Viral; Hepadnaviridae; Hepadnaviridae Infections; Hepatocytes; Humans; Orthohepadnavirus; Phylogeny; Sequence Alignment; Shrews; Viral Proteins
PubMed: 30884426
DOI: 10.1016/j.virol.2019.03.007 -
Proceedings of the National Academy of... Jun 2017
Topics: Hepatitis A virus; Hepatitis B virus; Humans
PubMed: 28607085
DOI: 10.1073/pnas.1707142114 -
Gut Aug 2017
Topics: Carcinoma, Hepatocellular; Hepatitis B virus; Liver Neoplasms
PubMed: 28100646
DOI: 10.1136/gutjnl-2016-313462 -
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 -
Bacteriophages and their applications in the diagnosis and treatment of hepatitis B virus infection.World Journal of Gastroenterology Sep 2014Hepatitis B virus (HBV) infection is a major global health challenge leading to serious disorders such as cirrhosis and hepatocellular carcinoma. Currently, there exist... (Review)
Review
Hepatitis B virus (HBV) infection is a major global health challenge leading to serious disorders such as cirrhosis and hepatocellular carcinoma. Currently, there exist various diagnostic and therapeutic approaches for HBV infection. However, prevalence and hazardous effects of chronic viral infection heighten the need to develop novel methodologies for the detection and treatment of this infection. Bacteriophages, viruses that specifically infect bacterial cells, with a long-established tradition in molecular biology and biotechnology have recently been introduced as novel tools for the prevention, diagnosis and treatment of HBV infection. Bacteriophages, due to tremendous genetic flexibility, represent potential to undergo a huge variety of surface modifications. This property has been the rationale behind introduction of phage display concept. This powerful approach, together with combinatorial chemistry, has shaped the concept of phage display libraries with diverse applications for the detection and therapy of HBV infection. This review aims to offer an insightful overview of the potential of bacteriophages in the development of helpful prophylactic (vaccine design), diagnostic and therapeutic strategies for HBV infection thereby providing new perspectives to the growing field of bacteriophage researches directing towards HBV infection.
Topics: Animals; Antiviral Agents; Bacteriophages; Cell Surface Display Techniques; Drug Design; Gene Expression Regulation, Viral; Genotype; Hepatitis B; Hepatitis B Vaccines; Hepatitis B virus; Humans; Molecular Targeted Therapy; Predictive Value of Tests
PubMed: 25206272
DOI: 10.3748/wjg.v20.i33.11671 -
Yakugaku Zasshi : Journal of the... 2019The development of antiviral agents enables the control of chronic infectious diseases caused by infection with herpesviruses, human immunodeficiency virus, and... (Review)
Review
The development of antiviral agents enables the control of chronic infectious diseases caused by infection with herpesviruses, human immunodeficiency virus, and hepatitis C virus. In contrast, antiviral treatment against hepatitis B virus (HBV) infection remains a significant area for improvement. One of the main barriers hampering the progress of HBV research has been a lack of cell culture systems efficiently reproducing the viral proliferation process. Recently, cell line-based HBV infection systems have been developed which are useful to analyze the mechanisms of HBV replication and to screen for new anti-HBV agents. In this article, we summarize the establishment of such cell models and the identification of small molecules that inhibit the HBV entry process and discuss their future potential as a novel class of anti-HBV agents.
Topics: Antiviral Agents; Cell Culture Techniques; Cells, Cultured; Drug Discovery; Drug Evaluation, Preclinical; Hepatitis B; Hepatitis B virus; Humans; Virus Replication
PubMed: 30606935
DOI: 10.1248/yakushi.18-00164-4 -
Pathologie-biologie Aug 2010The hepatitis B virus (HBV) is a widespread human pathogen and a major health problem in many countries. Molecular cloning and sequencing of the viral DNA genome has... (Review)
Review
The hepatitis B virus (HBV) is a widespread human pathogen and a major health problem in many countries. Molecular cloning and sequencing of the viral DNA genome has demonstrated a small and compact structure organized into four overlapping reading frames that encode the viral proteins. Besides structural proteins of the core and the envelope, HBV encodes a DNA polymerase with reverse transcriptase activity, a secreted antigen of unknown function, and a transcriptional activator that is essential for viral replication. Major steps of the viral life cycle have been unraveled, including transcription of all viral RNAs from nuclear covalently closed circular DNA (cccDNA), followed by encapsidation of pregenomic RNA, a more-than-genome length transcript, and reverse transcription of pregenomic RNA leading to asymmetric synthesis of the DNA strands. Although HBV has been recognized as a human tumor virus, no direct transforming activity could be evidenced in different cellular and animal models. However, the transcriptional regulatory protein HBx encoded by the X gene is endowed with weak oncogenic activity. HBx harbors pleiotropic activities and plays a major role in HBV pathogenesis and in liver carcinogenesis.
Topics: DNA, Viral; Genome, Viral; Hepatitis B virus; Humans; Trans-Activators; Transcription, Genetic; Viral Regulatory and Accessory Proteins; Virus Replication
PubMed: 20483545
DOI: 10.1016/j.patbio.2010.03.005 -
Viruses Mar 2021Chronic hepatitis B virus (HBV) causes serious clinical problems, such as liver cirrhosis and hepatocellular carcinoma. Current antiviral treatments suppress HBV;... (Review)
Review
Chronic hepatitis B virus (HBV) causes serious clinical problems, such as liver cirrhosis and hepatocellular carcinoma. Current antiviral treatments suppress HBV; however, the clinical cure rate remains low. Basic research on HBV is indispensable to eradicate and cure HBV. Genetic alterations are defined by nucleotide substitutions and canonical forms of structural variations (SVs), such as insertion, deletion and duplication. Additionally, genetic changes inconsistent with the canonical forms have been reported, and these have been termed complex SVs. Detailed analyses of HBV using bioinformatical applications have detected complex SVs in HBV genomes. Sequence gaps and low sequence similarity have been observed in the region containing complex SVs. Additionally, insertional motif sequences have been observed in HBV strains with complex SVs. Following the analyses of complex SVs in the HBV genome, the role of SVs in the genetic diversity of orthohepadnavirus has been investigated. SV polymorphisms have been detected in comparisons of several species of orthohepadnaviruses. As mentioned, complex SVs are composed of multiple SVs. On the contrary, SV polymorphisms are observed as insertions of different SVs. Up to a certain point, nucleotide substitutions cause genetic differences. However, at some point, the nucleotide sequences are split into several particular patterns. These SVs have been observed as polymorphic changes. Different species of orthohepadnaviruses possess SVs which are unique and specific to a certain host of the virus. Studies have shown that SVs play an important role in the HBV genome. Further studies are required to elucidate their virologic and clinical roles.
Topics: DNA, Viral; Gene Rearrangement; Genome, Viral; Hepatitis B; Hepatitis B virus; Humans; Mutation; Polymorphism, Genetic
PubMed: 33809245
DOI: 10.3390/v13030473 -
Archives of Virology Feb 2018Perinatal transmission is one of the most common routes of hepatitis B virus (HBV) transmission. This study aims to identify the epidemiological features of HBV among... (Meta-Analysis)
Meta-Analysis Review
Perinatal transmission is one of the most common routes of hepatitis B virus (HBV) transmission. This study aims to identify the epidemiological features of HBV among pregnant Iranian women. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two authors independently searched several online databases without time limit until May 2017. The databases include Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed, Science Direct, Cochrane, Web of Science and Google Scholar. The data were analyzed based on a random-effects model using Comprehensive Meta-Analysis software version 2. Thirty-seven studies were included in the meta-analysis. The prevalence of HBV among pregnant Iranian women was 1.18% (95% CI: 0.09%-1.53%). The prevalence of HBV among pregnant women living in urban and rural areas was 1.60% (95% CI: 0.06%-4.30%) and 1.70% (95% CI: 0.09%-3.2%), respectively. The prevalence of HBV among housewives and working pregnant women was 4.3% (95% CI: 1.4%-12.5%) and 1.2% (95% CI: 0.02%-5.8%), respectively. The risk of developing an HBV infection was significantly associated with illiteracy (p = 0.013), abortion (p = 0.001), blood transfusion (p < 0.001) and addicted spouse (p = 0.045). However, no significant relationship was observed between HBV infection and urbanization (p = 0.65), occupation (p = 0.37), history of surgery (p = 0.32) or tattooing (p = 0.69). Vaccination coverage (receiving at least a single dose) in pregnant women was 9.8% (95% CI: 5.3%-17.5%). The prevalence of HBV among pregnant women is lower than in the general population of Iran. HBV vaccination coverage was low among pregnant Iranian women. Therefore, health policy-makers are recommended to enforce immunization programs for HBV vaccination among high-risk pregnant women.
Topics: Female; Hepatitis B; Hepatitis B virus; Humans; Infectious Disease Transmission, Vertical; Iran; Pregnancy; Pregnancy Complications, Infectious; Prevalence
PubMed: 29063378
DOI: 10.1007/s00705-017-3551-6 -
Expert Review of Proteomics Feb 2014Hepatitis B virus (HBV) is a small and enveloped DNA virus, of which chronic infection is the main risk factor of liver cirrhosis and hepatocellular carcinoma. Hepatitis... (Review)
Review
Hepatitis B virus (HBV) is a small and enveloped DNA virus, of which chronic infection is the main risk factor of liver cirrhosis and hepatocellular carcinoma. Hepatitis B virus X protein (HBx) is a multifunctional protein encoded by HBV genome, which have significant effects on HBV replication and pathogenesis. Through directly interacting with cellular proteins, HBx is capable to promote HBV replication, regulate transcription of host genes, disrupt protein degradation, modulate signaling pathway, manipulate cell death and deregulate cell cycle. In this review, we briefly discuss the diversified effects of HBx-interactome and their potential clinical significances.
Topics: Animals; Biomedical Research; Cell Cycle; Cell Death; Hepatitis B virus; Host-Pathogen Interactions; Humans; Proteome; Proteomics; Signal Transduction; Trans-Activators; Transcriptional Activation; Viral Regulatory and Accessory Proteins
PubMed: 24308553
DOI: 10.1586/14789450.2014.861745