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Viruses Sep 2021Hepatitis D is the smallest virus known to infect humans, the most aggressive, causing the most severe disease. It is considered a satellite or defective virus requiring... (Review)
Review
Hepatitis D is the smallest virus known to infect humans, the most aggressive, causing the most severe disease. It is considered a satellite or defective virus requiring the hepatitis B surface antigen (HBsAg) for its replication with approximately 10-70 million persons infected. Elimination of hepatitis D is, therefore, closely tied to hepatitis B elimination. There is a paucity of quality data in many resource-poor areas. Despite its aggressive natural history, treatment options for hepatitis D to date have been limited and, in many places, inaccessible. For decades, Pegylated interferon alpha (Peg IFN α) offered limited response rates (20%) where available. Developments in understanding viral replication pathways has meant that, for the first time in over three decades, specific therapy has been licensed for use in Europe. Bulevirtide (Hepcludex) is an entry inhibitor approved for use in patients with confirmed viraemia and compensated disease. It can be combined with Peg IFN α and/or nucleos(t)ide analogue for hepatitis B. Early reports suggest response rates of over 50% with good tolerability profile. Additional agents showing promise include the prenylation inhibitor lonafarnib, inhibitors of viral release (nucleic acid polymers) and better tolerated Peg IFN lambda (λ). These agents remain out of reach for most resource limited areas where access to new therapies are delayed by decades. strategies to facilitate access to care for the most vulnerable should be actively sought by all stakeholders.
Topics: Antiviral Agents; Drug Therapy, Combination; Europe; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis D; Humans; Interferon-alpha; Lipopeptides; Piperidines; Pyridines; Treatment Outcome; Viral Load; Virus Replication
PubMed: 34696341
DOI: 10.3390/v13101912 -
World Journal of Gastroenterology Jun 2020Hepatitis D virus (HDV) is a global health threat with more than 15 million humans affected. Current treatment options are largely unsatisfactory leaving chronically... (Review)
Review
Hepatitis D virus (HDV) is a global health threat with more than 15 million humans affected. Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular carcinoma. HDV is the only human satellite virus known. It encodes only two proteins, and requires Hepatitis B virus (HBV) envelope protein expression for productive virion release and spread of the infection. How HDV could evolve and why HBV was selected as a helper virus remains unknown. Since the discovery of Na-taurocholate co-transporting polypeptide as the essential uptake receptor for HBV and HDV, we are beginning to understand the interactions of HDV and the immune system. While HBV is mostly regarded a stealth virus, that escapes innate immune recognition, HBV-HDV coinfection is characterized by a strong innate immune response. Cytoplasmic RNA sensor melanoma differentiation antigen 5 has been reported to recognize HDV RNA replication and activate innate immunity. Innate immunity, however, seems not to impair HDV replication while it inhibits HBV. In this review, we describe what is known up-to-date about the interplay between HBV as a helper and HDV's immune evasion strategy and identify where additional research is required.
Topics: Carcinoma, Hepatocellular; Coinfection; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis D, Chronic; Hepatitis Delta Virus; Hepatitis delta Antigens; Humans; Immune Evasion; Immunity, Innate; Interferon-Induced Helicase, IFIH1; Liver; Liver Cirrhosis; Liver Neoplasms; Organic Anion Transporters, Sodium-Dependent; RNA, Viral; Receptors, Pattern Recognition; Satellite Viruses; Symporters; Virus Replication
PubMed: 32550754
DOI: 10.3748/wjg.v26.i21.2781 -
Database : the Journal of Biological... Dec 2021To date, various studies have found that the occurrence of cancer may be related to viral infections. Therefore, it is important to explore the relationship between...
To date, various studies have found that the occurrence of cancer may be related to viral infections. Therefore, it is important to explore the relationship between viruses and diseases. The International Agency for Research on Cancer has defined six types of viruses as Class 1 human carcinogens, including Epstein-Barr virus, hepatitis C virus, hepatitis B virus, human T-cell lymphotropic virus, human herpesvirus 8 and human papillomavirus, while Merkel cell polyomavirus is classified as 'probably carcinogenic to humans' (Group 2A). Therefore, in-depth research on these viruses will help clarify their relationship with diseases, and substantial efforts have been made to sequence their genomes. However, there is no complete database documenting these cancer-associated viruses, and researchers are not able to easily access and retrieve the published genomes. In this study, we developed iCAV, a database that integrates the genomes of cancer-related viruses and the corresponding phenotypes. We collected a total of 18 649 genome sequences from seven human disease-related viruses, and each virus was further classified by the associated disease, sample and country. iCAV is a comprehensive resource of cancer-associated viruses that provides browse and download functions for viral genomes. Database URL: http://icav.omicsbio.info/.
Topics: Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Neoplasms; Satellite Viruses; Viruses
PubMed: 34907423
DOI: 10.1093/database/baab079 -
Journal of Hepatology Apr 2017
Topics: Antiviral Agents; Hepatitis B; Hepatitis B virus; Hepatitis Delta Virus; Organic Anion Transporters, Sodium-Dependent; Virus Internalization
PubMed: 27965159
DOI: 10.1016/j.jhep.2016.11.028 -
World Journal of Gastroenterology Aug 2015Hepatitis D virus (HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsid... (Review)
Review
Hepatitis D virus (HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsid antigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide (NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs (NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated preS1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP's metabolic function. These drugs may have a role in HDV treatment. Interference with host-mediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem I regions can inhibit genomic HDV ribozyme activity.
Topics: Antiviral Agents; Drug Therapy, Combination; Hepatitis D; Hepatitis Delta Virus; Host-Pathogen Interactions; Humans; Molecular Targeted Therapy; Oligonucleotides, Antisense; Protein Prenylation; Treatment Outcome; Virus Internalization
PubMed: 26327754
DOI: 10.3748/wjg.v21.i32.9461 -
International Journal of Molecular... Mar 2022Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and... (Review)
Review
Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and D, although these diseases are caused by very different viruses. Paired with the conventional study of protein-host interactions, the rapid technological development of -omics and bioinformatics has allowed highlighting the important role of signaling networks in viral pathogenesis. In this review, we provide an integrated look on the three major viruses associated with chronic viral hepatitis in patients, summarizing similarities and differences in virus-induced cellular signaling relevant to the viral life cycles and liver disease progression.
Topics: Carcinoma, Hepatocellular; Chlamydia Infections; Hepatitis B; Hepatitis B virus; Hepatitis Delta Virus; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Liver Neoplasms
PubMed: 35269929
DOI: 10.3390/ijms23052787 -
BMC Infectious Diseases Aug 2023The geographical distribution of hepatitis B virus (HBV) and hepatitis D virus (HDV) genotypes is uneven and has its own clinical and organizational implications for... (Clinical Trial)
Clinical Trial
BACKGROUND
The geographical distribution of hepatitis B virus (HBV) and hepatitis D virus (HDV) genotypes is uneven and has its own clinical and organizational implications for health systems. Despite the introduction of vaccination and successful antiviral therapy the prevalence of chronic hepatitis B (with or without delta agent) increased over the past 5 years. This study aimed for the first time to investigate the molecular epidemiology of HBV and HDV in Kazakhstan.
METHODS
Total 834 chronic hepatitis B (with or without delta agent) patients were included to the study from November 2017 to June 2019. The material was collected from the regional hepatological сenters from 13 cities of Kazakhstan. Genotyping of HBV/HDV isolates was carried out using phylogenetic analysis of null-binary sequences of Kazakhstani isolates, in comparison with the reference sequences. Nucleotide sequence alignment was performed using the ClustalW algorithm, the "neighbor-joining" method was used for the construction of phylogenetic trees and subsequent analysis.
RESULTS
Overall 341 samples were PCR-positive and genotyped for HBV. Comparison and phylogenetic analysis of nucleotide sequences of HBV isolates showed that they were represented by genotypes HBV-D (95.9%), HBV-A (3.5%) and HBV-C (0.6%). At the same time, the identity of the nucleotide sequences of Kazakhstani isolates were: HBV-D (95-100%); HBV-A (97.2-100%) and HBV-C (99%). 256 samples were PCR positive and genotyped for HDV, all of them belonged to genotype 1.
CONCLUSION
This study describes for the first time the molecular epidemiology of HBV and HDV in Kazakhstan. The data obtained expand the knowledge of the global epidemiology of viruses; have potential implications for public health policy and for further clinical research on chronic hepatitis in Kazakhstan.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05095181 (registered on 27/10/2021).
Topics: Humans; Genotype; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis D; Hepatitis Delta Virus; Kazakhstan; Phylogeny; Prevalence
PubMed: 37580657
DOI: 10.1186/s12879-023-08524-1 -
Viruses May 2023RNA viruses may be monopartite (all genes on one strand), multipartite (two or more strands packaged separately) or segmented (two or more strands packaged together). In...
RNA viruses may be monopartite (all genes on one strand), multipartite (two or more strands packaged separately) or segmented (two or more strands packaged together). In this article, we consider competition between a complete monopartite virus, A, and two defective viruses, D and E, that have complementary genes. We use stochastic models that follow gene translation, RNA replication, virus assembly, and transmission between cells. D and E multiply faster than A when stored in the same host as A or when together in the same host, but they cannot multiply alone. D and E strands are packaged as separate particles unless a mechanism evolves that allows assembly of D + E segmented particles. We show that if defective viruses assemble rapidly into separate particles, the formation of segmented particles is selected against. In this case, D and E spread as parasites of A, and the bipartite D + E combination eliminates A if the transmissibility is high. Alternatively, if defective strands do not assemble rapidly into separate particles, then a mechanism for assembly of segmented particles is selected for. In this case, the segmented virus can eliminate A if transmissibility is high. Conditions of excess protein resources favor bipartite viruses, while conditions of excess RNA resources favor segmented viruses. We study the error threshold behavior that arises when deleterious mutations are introduced. Relative to bipartite and segmented viruses, deleterious mutations favor monopartite viruses. A monopartite virus can give rise to either a bipartite or a segmented virus, but it is unlikely that both will originate from the same virus.
Topics: Viruses; RNA Viruses; Virus Assembly
PubMed: 37243221
DOI: 10.3390/v15051135 -
Journal of Clinical and Translational... Sep 2015The mechanisms determining persistence of hepatitis B virus (HBV) infection and long-term pathogenesis of HBV-associated liver disease appear to be multifactorial.... (Review)
Review
The mechanisms determining persistence of hepatitis B virus (HBV) infection and long-term pathogenesis of HBV-associated liver disease appear to be multifactorial. Although viral replication can be efficiently suppressed by the antiviral treatments currently available, viral clearance is generally not achieved since HBV has developed unique replication strategies, enabling persistence of its genome within the infected hepatocytes. Moreover, no direct antiviral therapy exists for the more than 15 million people worldwide that are also coinfected with the hepatitis delta virus (HDV), a defective virus that needs the HBV envelope proteins for propagation. The limited availability of robust HBV and HDV infection systems has hindered the understanding of the complex network of virus-virus and virus-host interactions that are established in the course of infection and slowed down progress in drug development. Since chronic HBV/HDV coinfection leads to the most severe form of chronic viral hepatitis, elucidation of the molecular mechanisms regulating virus-host interplay and pathogenesis are urgently needed. This article summarizes the current knowledge regarding the interactions among HBV, HDV, and the infected target cell and discusses the dependence of HDV on HBV activity and possible future therapeutic approaches.
PubMed: 26623269
DOI: 10.14218/JCTH.2015.00018 -
Australian Journal of General Practice Aug 2023Hepatitis D virus (HDV) requires the presence of hepatitis B virus for replication and infection, and is associated with accelerated progression to cirrhosis and an...
BACKGROUND
Hepatitis D virus (HDV) requires the presence of hepatitis B virus for replication and infection, and is associated with accelerated progression to cirrhosis and an increased risk of hepatocellular carcinoma. Approximately 4% of Australians living with hepatitis B are infected with HDV, although it is likely that HDV remains underdiagnosed.
OBJECTIVE
This paper highlights the importance of screening for HDV in patients living with chronic hepatitis B (CHB) and provides an overview of diagnosis and treatment approaches for general practitioners (GPs), with the hope of reducing preventable liver-related morbidity and mortality in people living with CHB and HDV coinfection.
DISCUSSION
The diversity of risk factors and geographical origins of patients in the multicultural Australian populace highlights the need for routine testing for HDV in patients diagnosed with CHB. GPs have a pivotal role in the diagnosis of HDV and should, if possible, promptly refer patients to non-GP specialist physicians to consider HDV therapy.
Topics: Humans; Australia; Hepatitis D; Hepatitis Delta Virus; Liver Neoplasms; General Practice
PubMed: 37532443
DOI: 10.31128/AJGP-08-22-6516