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Clinical Medicine (London, England) Jul 2023Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can... (Review)
Review
Hepatitis D virus (HDV), also referred to as hepatitis delta virus, is the smallest virus capable of causing human disease. It is unable to replicate on its own and can only propagate in the presence of hepatitis B virus (HBV). Infection with both HBV and HDV frequently results in more severe disease than HBV alone, with higher instances of cirrhosis, liver failure and hepatocellular carcinoma (HCC). Thus, there is a need for effective treatment for HDV; however, currently approved treatment options are very limited both in terms of their efficacy and availability. This makes the management of HDV a challenge for physicians. In this review, we look at the background, diagnosis and treatment of HDV, informed by our hospital data, to set out the optimal management of HDV; we also explore novel treatment options for this disease.
Topics: Humans; Hepatitis Delta Virus; Antiviral Agents; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis B virus
PubMed: 37353306
DOI: 10.7861/clinmed.2022-0556 -
Trends in Microbiology Jul 2020Viral defective interfering particles (DIPs) were intensely studied several decades ago but research waned leaving open many critical questions. New technologies and... (Review)
Review
Viral defective interfering particles (DIPs) were intensely studied several decades ago but research waned leaving open many critical questions. New technologies and other advances led to a resurgence in DIP studies for negative-strand RNA viruses. While DIPs have long been recognized, their exact contribution to the outcome of acute or persistent viral infections has remained elusive. Recent studies have identified defective viral genomes (DVGs) in human infections, including respiratory syncytial virus and influenza, and growing evidence indicates that DVGs influence disease severity and may contribute to viral persistence. Further, several studies have advanced our understanding of key viral and host factors that regulate DIP formation and activity. Here we review these discoveries and highlight key questions moving forward.
Topics: Defective Viruses; Gene Deletion; Genome, Viral; Orthomyxoviridae; Respiratory Syncytial Viruses; Viral Interference; Virus Replication
PubMed: 32544442
DOI: 10.1016/j.tim.2020.02.006 -
Journal of Hepatology Apr 2016Hepatitis delta virus (HDV) is a defective virus and a satellite of the hepatitis B virus (HBV). Its RNA genome is unique among animal viruses, but it shares common... (Review)
Review
Hepatitis delta virus (HDV) is a defective virus and a satellite of the hepatitis B virus (HBV). Its RNA genome is unique among animal viruses, but it shares common features with some plant viroids, including a replication mechanism that uses a host RNA polymerase. In infected cells, HDV genome replication and formation of a nucleocapsid-like ribonucleoprotein (RNP) are independent of HBV. But the RNP cannot exit, and therefore propagate, in the absence of HBV, as the latter supplies the propagation mechanism, from coating the HDV RNP with the HBV envelope proteins for cell egress to delivery of the HDV virions to the human hepatocyte target. HDV is therefore an obligate satellite of HBV; it infects humans either concomitantly with HBV or after HBV infection. HDV affects an estimated 15 to 20 million individuals worldwide, and the clinical significance of HDV infection is more severe forms of viral hepatitis--acute or chronic--, and a higher risk of developing cirrhosis and hepatocellular carcinoma in comparison to HBV monoinfection. This review covers molecular aspects of HDV replication cycle, including its interaction with the helper HBV and the pathogenesis of infection in humans.
Topics: Hepatitis D; Hepatitis Delta Virus; Hepatocytes; Humans; RNA, Viral; Virion; Virus Replication
PubMed: 27084031
DOI: 10.1016/j.jhep.2016.02.013 -
Biotechnology Journal May 2015Defective interfering particles (DIPs) have been found for many important viral pathogens and it is believed that most viruses generate DIPs. This article reviews the... (Review)
Review
Defective interfering particles (DIPs) have been found for many important viral pathogens and it is believed that most viruses generate DIPs. This article reviews the current knowledge of the generation and amplification of DIPs, which possess deletions in the viral genome but retain the ability to replicate in the presence of a complete helper virus. In addition, mechanisms are discussed by which DIPs interfere with the replication of their helper virus leading to the production of mainly progeny DIPs by coinfected cells. Even though DIPs cannot replicate on their own, they are biologically active and it is well known that they have a huge impact on virus replication, evolution, and pathogenesis. Moreover, defective genomes are potent inducers of the innate immune response. Yet, little attention has been paid to DIPs in recent years and their impact on biotechnological products such as vaccines and viral vectors remains elusive in most cases. With a focus on influenza virus, this review demonstrates that DIPs are important for basic research on viruses and for the production of viral vaccines and vectors. Reducing the generation and/or amplification of DIPs ensures reproducible results as well as high yields and consistent product quality in virus production.
Topics: Animals; Biotechnology; Genetic Vectors; Helper Viruses; Humans; Satellite Viruses; Viral Vaccines; Virus Replication
PubMed: 25728309
DOI: 10.1002/biot.201400429 -
Nature Microbiology Jul 2019Viruses survive often harsh host environments, yet we know little about the strategies they utilize to adapt and subsist given their limited genomic resources. We are... (Review)
Review
Viruses survive often harsh host environments, yet we know little about the strategies they utilize to adapt and subsist given their limited genomic resources. We are beginning to appreciate the surprising versatility of viral genomes and how replication-competent and -defective virus variants can provide means for adaptation, immune escape and virus perpetuation. This Review summarizes current knowledge of the types of defective viral genomes generated during the replication of RNA viruses and the functions that they carry out. We highlight the universality and diversity of defective viral genomes during infections and discuss their predicted role in maintaining a fit virus population, their impact on human and animal health, and their potential to be harnessed as antiviral tools.
Topics: Adjuvants, Immunologic; Animals; Antiviral Agents; Biological Evolution; Defective Viruses; Genome, Viral; Host-Pathogen Interactions; Humans; RNA Viruses; Virus Replication
PubMed: 31160826
DOI: 10.1038/s41564-019-0465-y -
Viruses Aug 2023Hepatitis D virus (HDV) is a defective RNA virus with a negative-strand RNA genome encompassing less than 1700 nucleotides. The HDV genome encodes only for one protein,... (Review)
Review
Hepatitis D virus (HDV) is a defective RNA virus with a negative-strand RNA genome encompassing less than 1700 nucleotides. The HDV genome encodes only for one protein, the hepatitis delta antigen (HDAg), which exists in two forms acting as nucleoproteins. HDV depends on the envelope proteins of the hepatitis B virus as a helper virus for packaging its ribonucleoprotein complex (RNP). HDV is considered the causative agent for the most severe form of viral hepatitis leading to liver fibrosis/cirrhosis and hepatocellular carcinoma. Many steps of the life cycle of HDV are still enigmatic. This review gives an overview of the complete life cycle of HDV and identifies gaps in knowledge. The focus is on the description of cellular factors being involved in the life cycle of HDV and the deregulation of cellular pathways by HDV with respect to their relevance for viral replication, morphogenesis and HDV-associated pathogenesis. Moreover, recent progress in antiviral strategies targeting cellular structures is summarized in this article.
Topics: Animals; Hepatitis Delta Virus; Hepatitis delta Antigens; Antiviral Agents; Life Cycle Stages; Liver Cirrhosis; Liver Neoplasms
PubMed: 37632029
DOI: 10.3390/v15081687 -
Virus Genes Feb 2021Plant viral satellites fall under the category of subviral agents. Their genomes are composed of small RNA or DNA molecules a few hundred nucleotides in length and... (Review)
Review
Plant viral satellites fall under the category of subviral agents. Their genomes are composed of small RNA or DNA molecules a few hundred nucleotides in length and contain an assortment of highly complex and overlapping functions. Each lacks the ability to either replicate or undergo encapsidation or both in the absence of a helper virus (HV). As the number of known satellites increases steadily, our knowledge regarding their sequence conservation strategies, means of replication and specific interactions with host and helper viruses is improving. This review demonstrates that the molecular interactions of these satellites are unique and highly complex, largely influenced by the highly specific host plants and helper viruses that they associate with. Circularized forms of single-stranded RNA are of particular interest, as they have recently been found to play a variety of novel cellular functions. Linear forms of satRNA are also of great significance as they may complement the helper virus genome in exacerbating symptoms, or in certain instances, actively compete against it, thus reducing symptom severity. This review serves to describe the current literature with respect to these molecular mechanisms in detail as well as to discuss recent insights into this emerging field in terms of evolution, classification and symptom development. The review concludes with a discussion of future steps in plant viral satellite research and development.
Topics: DNA, Satellite; DNA, Viral; Helper Viruses; Host Microbial Interactions; Plant Diseases; Plant Viruses; RNA, Satellite; RNA, Viral; Satellite Viruses; Virus Replication
PubMed: 33226576
DOI: 10.1007/s11262-020-01806-9 -
Antiviral Research Jul 2020Hepatitis B Virus (HBV) that infects liver parenchymal cells is responsible for severe liver diseases and co-infection with Hepatitis Delta Virus (HDV) leads to the most... (Review)
Review
Hepatitis B Virus (HBV) that infects liver parenchymal cells is responsible for severe liver diseases and co-infection with Hepatitis Delta Virus (HDV) leads to the most aggressive form of viral hepatitis. Even tough being different for their viral genome (relaxed circular partially double stranded DNA for HBV and circular RNA for HDV), HBV and HDV are both maintained as episomes in the nucleus of infected cells and use the cellular machinery for the transcription of their viral RNAs. We propose here an update on the current knowledge on HDV replication cycle that may eventually help to identify new antiviral targets.
Topics: Animals; Cell Nucleus; Coinfection; Genome, Viral; Hepatitis B virus; Hepatitis Delta Virus; Hepatitis, Viral, Human; Hepatocytes; Humans; Mice; Plasmids; Virus Replication
PubMed: 32360949
DOI: 10.1016/j.antiviral.2020.104812 -
Zhonghua Gan Zang Bing Za Zhi =... Oct 2022Hepatitis D virus (HDV) is a defective RNA virus with 8 genotypes, which requires hepatitis B virus (HBV) for its replication both in co-infection (HDV infection occurs... (Review)
Review
Hepatitis D virus (HDV) is a defective RNA virus with 8 genotypes, which requires hepatitis B virus (HBV) for its replication both in co-infection (HDV infection occurs when people become infected with both hepatitis B and D simultaneously) and super-infection (HDV infection after infected with hepatitis B). Due to persistency of anti-HDV in the superinfected patient, the most epidemiology data of HDV infection suggests HBV/HDV super-infection. Because of inadequate awareness and effective HBV vaccination programme, HDV infection screen was not specific recommended, except for risk population recommended by AASLD. However, the disease burden of HDV infection was not fully understood and might be underestimated. This review summarized the anti-HDV and HDV genotype epidemiology and the screening of HDV infection.
Topics: Humans; Hepatitis D; Hepatitis Delta Virus; Hepatitis B; Hepatitis B virus; Genotype; RNA, Viral; Coinfection
PubMed: 36727224
DOI: 10.3760/cma.j.cn501113-20221019-00498 -
Liver International : Official Journal... Feb 2020Around 15-20 million people develop chronic hepatitis delta virus worldwide. Hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the hepatitis... (Review)
Review
Around 15-20 million people develop chronic hepatitis delta virus worldwide. Hepatitis delta virus (HDV) is a defective RNA virus requiring the presence of the hepatitis B virus surface antigen (HBsAg) to complete its life cycle. HDV infects hepatocytes using the hepatitis B virus (HBV) receptor, the sodium taurocholate cotransporting polypeptide (NTCP). The HDV genome is a circular single-stranded RNA which encodes for a single hepatitis delta antigen (HDAg) that exists in two forms (S-HDAg and L-HDAg), and its replication is mediated by the host RNA polymerases. The HBsAg-coated HDV virions contain a ribonucleoprotein (RNP) formed by the RNA genome packaged with small and large HDAg. Farnesylation of the L-HDAg is the limiting step for anchoring this RNP to HBsAg, and thus for assembling, secreting and propagating virion particles. There is an important risk of morbidity and mortality caused by end-stage liver disease and hepatocellular carcinoma with HDV and current treatment is pegylated-interferon (PEG-IFN) for 48 weeks with no other options in patients who fail treatment. The ideal goal for HDV treatment is the clearance of HBsAg, but a reasonably achievable goal is a sustained HDV virological response (negative HDV RNA 6 months after stopping treatment). New drug development must take into account the interaction of HBV and HDV. In this review, we will present the new insights in the HDV life cycle that have led to the development of novel classes of drugs and discuss antiviral approaches in phase II and III of development: bulevirtide (entry inhibitor), lonafarnib, (prenylation inhibitor) and REP 2139 (HBsAg release inhibitor).
Topics: Antiviral Agents; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis Delta Virus; Hepatitis delta Antigens; Humans; RNA, Viral; Virus Replication
PubMed: 32077603
DOI: 10.1111/liv.14356