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Cold Spring Harbor Perspectives in... Aug 2015Entry of hepatitis B (HBV) and hepatitis D viruses (HDV) into a host cell represents the initial step of infection. This process requires multiple steps, including the... (Review)
Review
Entry of hepatitis B (HBV) and hepatitis D viruses (HDV) into a host cell represents the initial step of infection. This process requires multiple steps, including the low-affinity attachment of the virus to the cell surface, followed by high-affinity attachment to specific receptor(s), and subsequent endocytosis-mediated internalization. Within the viral envelope, the preS1 region is involved in receptor binding. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as an entry receptor of HBV and HDV by affinity purification using a preS1 peptide. NTCP is mainly or exclusively expressed in the liver, and this membrane protein is at least one of the factors determining the narrow species specificity and hepatotropism of HBV and HDV. However, there are likely other factors that mediate the species and tissue tropism of HBV. This review summarizes the current understanding of the mechanisms of HBV/HDV entry.
Topics: Female; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Male; Receptors, Virus; Species Specificity; Taurocholic Acid; Tropism; Viral Envelope Proteins; Virion; Virus Internalization
PubMed: 26238794
DOI: 10.1101/cshperspect.a021378 -
Journal of Hepatology Apr 2016For almost three decades following the discovery of the human Hepatitis B Virus (HBV) the early events of virus infection (attachment to hepatocytes, specific binding to... (Review)
Review
For almost three decades following the discovery of the human Hepatitis B Virus (HBV) the early events of virus infection (attachment to hepatocytes, specific binding to a receptor on hepatocytes) remained enigmatic. The gradual improvement of tissue culture systems for HBV has enabled the identification of viral determinants for viral infectivity and facilitated the discovery of the human sodium taurocholate co-transporting polypeptide (hNTCP) as a liver specific receptor of HBV and its satellite, the human Hepatitis Delta Virus (HDV). These findings are currently leading basic and clinical research activities in new directions. (1) Stable hNTCP-expressing cell lines have become a valuable platform to study the full HBV replication cycle from its native template, the cccDNA. (2) The suitability of NTCP complemented cell culture systems for high throughput screening approaches will facilitate identification of novel host factors involved in HBV replication (including those that determine the peculiar host specificity of HBV infection) and will enable identification and development of novel drug candidates for improved therapeutics. (3) Since NTCP is a major host-specific restriction factor for HBV and HDV, hNTCP-expressing animals provide the basis for future susceptible in vivo models. (4) The concept obtained with the entry inhibitor Myrcludex B demonstrates that NTCP is a suitable target for clinical interference with viral entry. This will foster further clinical approaches aiming at curative combination therapies.
Topics: Animals; Cell Line; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Hepatocytes; Humans; Virus Internalization
PubMed: 27084034
DOI: 10.1016/j.jhep.2016.02.011 -
Viruses Jun 2020Hepatitis delta virus (HDV) and hepatitis B virus (HBV) are blood-borne viruses that infect human hepatocytes and cause significant liver disease. Infections with HBV... (Review)
Review
Hepatitis delta virus (HDV) and hepatitis B virus (HBV) are blood-borne viruses that infect human hepatocytes and cause significant liver disease. Infections with HBV are more damaging when there is a coinfection with HDV. The genomes and modes of replication of these two viruses are fundamentally different, except for the fact that, in nature, HDV replication is dependent upon the envelope proteins of HBV to achieve assembly and release of infectious virus particles, ones that use the same host cell receptor. This review focuses on what has been found of the various ways, natural and experimental, by which HDV particles can be assembled and released. This knowledge has implications for the prevention and treatment of HDV infections, and maybe for an understanding of the origin of HDV.
Topics: Animals; Hepatitis D; Hepatitis Delta Virus; Humans; Virus Replication
PubMed: 32560053
DOI: 10.3390/v12060648 -
International Journal of Molecular... Dec 2022Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are highly prevalent viruses estimated to infect approximately 300 million people and 12-72 million people... (Review)
Review
Hepatitis B virus (HBV) and hepatitis delta virus (HDV) are highly prevalent viruses estimated to infect approximately 300 million people and 12-72 million people worldwide, respectively. HDV requires the HBV envelope to establish a successful infection. Concurrent infection with HBV and HDV can result in more severe disease outcomes than infection with HBV alone. These viruses can cause significant hepatic disease, including cirrhosis, fulminant hepatitis, and hepatocellular carcinoma, and represent a significant cause of global mortality. Therefore, a thorough understanding of these viruses and the immune response they generate is essential to enhance disease management. This review includes an overview of the HBV and HDV viruses, including life cycle, structure, natural course of infection, and histopathology. A discussion of the interplay between HDV RNA and HBV DNA during chronic infection is also included. It then discusses characteristics of the immune response with a focus on reactions to the antigenic hepatitis B surface antigen, including small, middle, and large surface antigens. This paper also reviews characteristics of the immune response to the hepatitis D antigen (including small and large antigens), the only protein expressed by hepatitis D. Lastly, we conclude with a discussion of recent therapeutic advances pertaining to these viruses.
Topics: Humans; Hepatitis Delta Virus; Virus Replication; Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis B Surface Antigens
PubMed: 36555623
DOI: 10.3390/ijms232415973 -
Viruses Apr 2021Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the... (Review)
Review
Hepatitis Delta virus (HDV) lies in between satellite viruses and viroids, as its unique molecular characteristics and life cycle cannot categorize it according to the standard taxonomy norms for viruses. Being a satellite virus of hepatitis B virus (HBV), HDV requires HBV envelope glycoproteins for its infection cycle and its transmission. HDV pathogenesis varies and depends on the mode of HDV and HBV infection; a simultaneous HDV and HBV infection will lead to an acute hepatitis that will resolve spontaneously in the majority of patients, whereas an HDV super-infection of a chronic HBV carrier will mainly result in the establishment of a chronic HDV infection that may progress towards cirrhosis, liver decompensation, and hepatocellular carcinoma (HCC). With this review, we aim to unravel Ariadne's thread into the labyrinth of acute and chronic HDV infection pathogenesis and will provide insights into the complexity of this exciting topic by detailing the different players and mechanisms that shape the clinical outcome.
Topics: Animals; Carcinoma, Hepatocellular; Coinfection; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis Delta Virus; Hepatitis delta Antigens; Humans; Liver Neoplasms; Mice; RNA, Viral; Satellite Viruses; Virus Replication
PubMed: 33924806
DOI: 10.3390/v13050778 -
Intervirology 2021Hepatitis delta virus (HDV) is considered a satellite virus that requires hepatitis B virus surface antigen for infectivity. HDV is endemic in some Pacific Island (PI)...
Hepatitis delta virus (HDV) is considered a satellite virus that requires hepatitis B virus surface antigen for infectivity. HDV is endemic in some Pacific Island (PI) countries, including Kiribati and Nauru, with a unique genotype 1, "Pacific clade." The aims of this study were to determine the HDV genotypes in New Zealand and investigate the link of strains to other PI countries and the rest of the world through phylogenetics. Sequencing and phylogenetic analyses were performed on 16 HDV-positive serum samples from 14 individuals collected between 2009 and 2014 at Auckland Hospital. Thirteen of 14 strains were confirmed as genotype 1 and 1 was genotype 5. Eleven of the 13 genotype 1 strains clustered with the Pacific clade. These were isolated from subjects born in Samoa, Kiribati, Tuvalu, and Niue. Another genotype 1 strain isolated from a Maori health-care worker clustered most closely with a European strain. There was an African genotype 1 and genotype 5 from African-born subjects with HIV coinfection. This study supports the probable transmission of HDV Pacific clade around the PI from Micronesia to Polynesia. The data also confirm the need to screen hepatitis B surface antigen-positive individuals for HDV.
Topics: Genotype; Hepatitis B; Hepatitis D; Hepatitis Delta Virus; Humans; New Zealand; Pacific Islands; Phylogeny
PubMed: 33647912
DOI: 10.1159/000513685 -
Seminars in Immunopathology Aug 2021Chronic infections with human hepatitis viruses continue to be a major health burden worldwide. Despite the availability of an effective prophylactic vaccine against the... (Review)
Review
Chronic infections with human hepatitis viruses continue to be a major health burden worldwide. Despite the availability of an effective prophylactic vaccine against the hepatitis B virus (HBV) and of antiviral agents efficiently suppressing HBV replication, more than 250 million people are currently chronically infected with this hepatotropic DNA virus, and resolution of chronic hepatitis B (CHB) is rarely achieved. Moreover, coinfection with the hepatitis D virus (HDV), a human RNA satellite virus requiring the envelope proteins of HBV for productive viral spreading, substantially aggravates the disease course of CHB. The molecular mechanisms by which these viruses interact with each other and with the intrinsic innate responses of the hepatocytes are not fully understood. While HBV appears to avoid innate immune recognition, HDV elicits a strong enhancement of innate responses. Notwithstanding, such induction does not hamper HDV replication but contributes to liver inflammation and pathogenesis. Intriguingly, HDV appears to influence the ability of T cells to recognize infected hepatocytes by boosting antigen presentation. This review focuses on current knowledge regarding how these viruses can shape and counteract the intrinsic innate responses of the hepatocytes, thus affecting the immune system and pathogenesis. Understanding the distinct strategies of persistence that HBV and HDV have evolved is central for advancing the development of curative therapies.
Topics: Hepatitis B; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Immunity, Innate; Inflammation; T-Lymphocytes
PubMed: 34019142
DOI: 10.1007/s00281-021-00864-x -
The Israel Medical Association Journal... Aug 2022Hepatitis D virus may cause a disease at various severities in the presence of hepatitis B virus, using hepatitis B surface antigen (HBsAg) on the external envelope in...
BACKGROUND
Hepatitis D virus may cause a disease at various severities in the presence of hepatitis B virus, using hepatitis B surface antigen (HBsAg) on the external envelope in its replication process. Thus, people identified with HBsAg in blood tests should also be tested for hepatitis D virus.
OBJECTIVES
To describe the situation of performance of blood tests for detection of hepatitis D virus in patients positive for hepatitis surface antigen during 9 years in a population with heterogeneous origins in the north region of Israel.
METHODS
We conducted a retrospective study using the database of Clalit Health Services.
RESULTS
We found 3367 people were positive for HBsAg during the study period; 613 (18%) were tested for hepatitis D. People who tested for hepatitis D were younger (47.3 ± 15 years vs. 50.5) and showed a higher rate of visiting the gastroenterology clinic (80.6% vs. 41%). The rate of positive blood tests for hepatitis D was too small for analysis, but it still demonstrated tendency for higher rates in the Ethiopian Jewish group.
CONCLUSIONS
The recommendation for performance of blood test for hepatitis D virus was followed to a small extent. Considering the ethnic diversity of the population in Israel, activities to raise rates of performance should be considered.
Topics: Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans; Retrospective Studies
PubMed: 35972014
DOI: No ID Found -
BioMed Research International 2021Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased...
Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, , , and , and 4 novel genes, namely, , , , and , which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Computational Biology; Data Mining; Gene Expression Regulation, Neoplastic; Hepatitis B; Hepatitis Delta Virus; Humans; Liver Neoplasms; Microarray Analysis; Neoplasm Proteins; Protein Interaction Maps
PubMed: 33564675
DOI: 10.1155/2021/1093702 -
Journal of the Formosan Medical... Nov 2006Hepatitis D virus (HDV) is a subviral satellite with hepatitis B virus (HBV) as its natural helper virus. After entry into hepatocytes, it utilizes host cellular enzymes... (Review)
Review
Hepatitis D virus (HDV) is a subviral satellite with hepatitis B virus (HBV) as its natural helper virus. After entry into hepatocytes, it utilizes host cellular enzymes to replicate by a double-rolling-circle mechanism. HDV is most often transmitted by contact with contaminated blood and body fluid, similar to HBV infection. Approximately 5% of the global HBV carriers are coinfected with HDV, leading to a total of 10-15 million HDV carriers worldwide. HDV infection can occur concurrently with HBV infection (coinfection) or in a patient with established HBV infection (superinfection). The pathogenesis of HDV remains controversial. A decline in the prevalence of both acute and chronic hepatitis D (CHD) has been observed worldwide. At present, therapy for chronic HDV infection is by the use of interferon-alpha. Compared to chronic hepatitis B or C, CHD treatment requires a higher dosage and a longer duration of treatment, and post-treatment relapses are common. In order to prevent the progression of CHD and its related morbidity and mortality, more effective treatments are needed.
Topics: Hepatitis D; Hepatitis Delta Virus; Humans
PubMed: 17098688
DOI: 10.1016/S0929-6646(09)60172-8