scholarly journals Interaction and Replication Activation of Genotype I and II Hepatitis Delta Antigens

2004 ◽  
Vol 78 (6) ◽  
pp. 2693-2700 ◽  
Author(s):  
Sheng-Chieh Hsu ◽  
Jaw-Ching Wu ◽  
I-Jane Sheen ◽  
Wan-Jr Syu
Keyword(s):  
Genotype I ◽  
Hepatitis Delta ◽  
Hepatitis D ◽  
Virus Surface ◽  
Delta Antigen ◽  
B Virus ◽  
Hepatitis Delta Antigen ◽  
Different Origins ◽  
Genotype Ii ◽  
Hdv Genotype

ABSTRACT The nucleotide sequences of hepatitis D viruses (HDV) vary 5 to 14% among isolates of the same genotype and 23 to 34% among different genotypes. The only viral-genome-encoded antigen, hepatitis delta antigen (HDAg), has two forms that differ in size. The small HDAg (HDAg-S) trans-activates viral replication, while the large form (HDAg-L) is essential for viral assembly. Previously, it has been shown that the packaging efficiency of HDAg-L is higher for genotype I than for genotype II. In this study, the question of whether other functional properties of the HDAgs are affected by genotype differences is addressed. By coexpression of the two antigens in HuH-7 cells followed by specific antibody precipitation, it was found that HDAgs of different origins interacted without genotypic discrimination. Moreover, in the presence of hepatitis B virus surface antigen, HDAg-S was incorporated into virion-like particles through interaction with HDAg-L without genotype restriction. As to the differences in replication activation of genotype I HDV RNA, all HDAg-S clones tested had some trans-activation activity, and this activity varied greatly among isolates. As to the support of HDV genotype II replication, only clones of HDAg-S from genotype II showed trans-activation activity, and this activity also varied among isolates. In conclusion, genotype has no effect on HDAg interaction and genotype per se only partly predicts how much the HDAg-S of an HDV isolate affects the replication of a second HDV isolate.

scholarly journals A Hepatitis B Surface Antigen Mutant That Lacks the Antigenic Loop Region Can Self-Assemble and Interact with the Large Hepatitis Delta Antigen

2002 ◽  
Vol 76 (19) ◽  
pp. 10060-10063 ◽  
Author(s):  
Brendan O'Malley ◽  
David Lazinski
Keyword(s):  
Hepatitis B ◽  
Surface Antigen ◽  
Self Assembly ◽  
Hepatitis B Surface Antigen ◽  
Hepatitis Delta ◽  
Virus Surface ◽  
Delta Antigen ◽  
Loop Region ◽  
B Virus ◽  
Hepatitis Delta Antigen

ABSTRACT A novel hepatitis B virus surface antigen mutant harboring a deletion of most of the major antigenic loop region was competent for self-assembly and secretion. Although the mutant protein was competent for interaction with and incorporation of free large hepatitis delta antigen, it was partially defective in hepatitis delta virus RNP incorporation.

scholarly journals Genotype-Specific Complementation of Hepatitis Delta Virus RNA Replication by Hepatitis Delta Antigen

1998 ◽  
Vol 72 (4) ◽  
pp. 2806-2814 ◽  
Author(s):  
John L. Casey ◽  
John L. Gerin
Keyword(s):  
Hepatitis Delta Virus ◽  
Rna Replication ◽  
Cdna Clones ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Genotype Iii ◽  
Delta Antigen ◽  
Hepatitis Delta Antigen ◽  
Hdv Genotype ◽  
Delta Virus

ABSTRACT Characterizations of genetic variations among hepatitis delta virus (HDV) isolates have focused principally on phylogenetic analysis of sequences, which vary by 30 to 40% among three genotypes and about 10 to 15% among isolates of the same genotype. The significance of the sequence differences has been unclear but could be responsible for pathogenic variations associated with the different genotypes. Studies of the mechanisms of HDV replication have been limited to cDNA clones from HDV genotype I, which is the most common. To perform a comparative analysis of HDV RNA replication in genotypes I and III, we have obtained a full-length cDNA clone from an HDV genotype III isolate. In transfected Huh-7 cells, the functional roles of the two forms of the viral protein, hepatitis delta antigen (HDAg), in HDV RNA replication are similar for both genotypes I and III; the short form is required for RNA replication, while the long form inhibits replication. For both genotypes, HDAg was able to support replication of RNAs of the same genotype that were mutated so as to be defective for HDAg production. Surprisingly, however, neither genotype I nor genotype III HDAg was able to support replication of such mutated RNAs of the other genotype. The inability of genotype III HDAg to support replication of genotype I RNA could have been due to a weak interaction between the RNA and HDAg. The clear genotype-specific activity of HDAg in supporting HDV RNA replication confirms the original categorization of HDV sequences in three genotypes and further suggests that these should be referred to as types (i.e., HDV-I and HDV-III) rather than genotypes.

scholarly journals A divergent hepatitis D-like agent in birds

2018 ◽  
Author(s):  
Michelle Wille ◽  
Hans J. Netter ◽  
Margaret Littlejohn ◽  
Lilly Yuen ◽  
Mang Shi ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Amino Acid Similarity ◽  
Hepatitis Delta ◽  
Hepatitis D ◽  
Delta Antigen ◽  
B Virus ◽  
Severe Liver Disease ◽  
Delta Virus

AbstractHepatitis delta virus (HDV) is currently only found in humans, and is a satellite virus that depends on hepatitis B virus (HBV) envelope proteins for assembly, release and entry. Using meta-transcriptomics, we identified the genome of a novel HDV-like agent in ducks. Sequence analysis revealed secondary structures that were shared with HDV, including self-complementarity and ribozyme features. The predicted viral protein shares 32% amino acid similarity to the small delta antigen of HDV and comprises a divergent phylogenetic lineage. The discovery of an avian HDV-like agent has important implications for the understanding of the origins of HDV and subviral agents.ImportanceHepatitis delta virus (HDV) is currently only found in humans, and coinfections of HDV and Hepatitis B virus (HBV) in humans result in severe liver disease. There are a number of hypotheses for the origin of HDV, although a key component of all is that HDV only exists in humans. Here, we describe a novel deltavirus-like agent identified in wild birds. Although this agent is genetically divergent, it exhibits important similarities to HDV, such as the presence of ribosymes and self-complementarity. The discovery of an avian HDV-like agent challenges our understanding of both the origin and the co-evolutionary relationships of subviral agents with helper viruses.

scholarly journals Hepatitis Delta Antigen Regulates mRNA and Antigenome RNA Levels during Hepatitis Delta Virus Replication

2019 ◽  
Vol 93 (8) ◽  
Author(s):  
Kaneemozhe Harichandran ◽  
Yiran Shen ◽  
Susannah Stephenson Tsoris ◽  
See-Chi Lee ◽  
John L. Casey
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis Delta Virus ◽  
Hepatitis Delta ◽  
Delta Antigen ◽  
B Virus ◽  
Hepatitis Delta Antigen ◽  
Infected Cells ◽  
Delta Virus

ABSTRACTHepatitis delta virus (HDV) is a satellite of hepatitis B virus that increases the severity of acute and chronic liver disease. HDV produces three processed RNAs that accumulate in infected cells: the circular genome; the circular antigenome, which serves as a replication intermediate; and lesser amounts of the mRNA, which encodes the sole viral protein, hepatitis delta antigen (HDAg). The HDV genome and antigenome RNAs form ribonucleoprotein complexes with HDAg. Although HDAg is required for HDV replication, it is not known how the relative amounts of HDAg and HDV RNA affect replication, or whether HDAg synthesis is regulated by the virus. Using a novel transfection system in which HDV replication is initiated usingin vitro-synthesized circular HDV RNAs, HDV replication was found to depend strongly on the relative amounts of HDV RNA and HDAg. HDV controls these relative amounts via differential effects of HDAg on the production of HDV mRNA and antigenome RNA, both of which are synthesized from the genome RNA template. mRNA synthesis is favored at low HDAg levels but becomes saturated at high HDAg concentrations. Antigenome RNA accumulation increases linearly with HDAg and dominates at high HDAg levels. These results provide a conceptual model for how HDV antigenome RNA production and mRNA transcription are controlled from the earliest stage of infection onward and also demonstrate that, in this control, HDV behaves similarly to other negative-strand RNA viruses, even though there is no genetic similarity between them.IMPORTANCEHepatitis delta virus (HDV) is a satellite of hepatitis B virus that increases the severity of liver disease; approximately 15 million people are chronically infected worldwide. There are no licensed therapies available. HDV is not related to any known virus, and few details regarding its replication cycle are known. One key question is whether and how HDV regulates the relative amounts of viral RNA and protein in infected cells. Such regulation might be important because the HDV RNA and protein form complexes that are essential for HDV replication, and the proper stoichiometry of these complexes could be critical for their function. Our results show that the relative amounts of HDV RNA and protein in cells are indeed important for HDV replication and that the virus does control them. These observations indicate that further study of these regulatory mechanisms is required to better understand replication of this serious human pathogen.

scholarly journals Large Hepatitis Delta Antigen Is a Novel Clathrin Adaptor-Like Protein

2007 ◽  
Vol 81 (11) ◽  
pp. 5985-5994 ◽  
Author(s):  
Cheng Huang ◽  
Shin C. Chang ◽  
I-Chen Yu ◽  
Yeou-Guang Tsay ◽  
Ming-Fu Chang
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Growth Factor Receptor ◽  
Endosomal Trafficking ◽  
Hepatitis Delta ◽  
Small Surface ◽  
Delta Antigen ◽  
B Virus ◽  
Hepatitis Delta Antigen ◽  
Clathrin Adaptor

ABSTRACT Clathrin-mediated endocytosis is a common pathway for viral entry, but little is known about the direct association of viral protein with clathrin in the cytoplasm. In this study, a putative clathrin box known to be conserved in clathrin adaptors was identified at the C terminus of the large hepatitis delta antigen (HDAg-L). Similar to clathrin adaptors, HDAg-L directly interacted with the N terminus of the clathrin heavy chain through the clathrin box. HDAg-L is a nucleocytoplasmic shuttle protein important for the assembly of hepatitis delta virus (HDV). Here, we demonstrated that brefeldin A and wortmannin, inhibitors of clathrin-mediated exocytosis and endosomal trafficking, respectively, specifically blocked HDV assembly but had no effect on the assembly of the small surface antigen of hepatitis B virus. In addition, cytoplasm-localized HDAg-L inhibited the clathrin-mediated endocytosis of transferrin and the degradation of epidermal growth factor receptor. These results indicate that HDAg-L is a new clathrin adaptor-like protein, and it may be involved in the maturation and pathogenesis of HDV coinfection or superinfection with hepatitis B virus through interaction with clathrin.

scholarly journals New Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against Hepatitis Delta Virus Using a Hepatitis Delta Antigen Derived from a Taiwanese Clone and Comparison to the Abbott Radioimmunoassay

2012 ◽  
Vol 19 (5) ◽  
pp. 817-819 ◽  
Author(s):  
Yung-Bin Kuo ◽  
Mei Chao ◽  
Yi-Hsuan Lee ◽  
Chau-Ting Yeh ◽  
Err-Cheng Chan
Keyword(s):  
Immunosorbent Assay ◽  
Hepatitis Delta Virus ◽  
Detection Efficiency ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hepatitis Delta ◽  
Hepatitis D ◽  
Delta Antigen ◽  
Hepatitis Delta Antigen ◽  
Hdv Infection ◽  
Delta Virus

ABSTRACTAn anti-hepatitis delta (HD) enzyme-linked immunosorbent assay (ELISA) using a specific recombinant hepatitis delta antigen derived from a local dominant hepatitis delta virus (hepatitis D virus; HDV) strain in Taiwan has been established. The detection efficiency of this assay was comparable to that of the commercially available Abbott anti-HD radioimmunoassay (RIA) and could be useful in routine laboratory diagnoses of HDV infection.

scholarly journals Hepatitis delta virus genotypes I and II cocirculate in an endemic area of Yakutia, Russia

2001 ◽  
Vol 82 (11) ◽  
pp. 2709-2718 ◽  
Author(s):  
Valeria Ivaniushina ◽  
Nadjia Radjef ◽  
Marfa Alexeeva ◽  
Elyanne Gault ◽  
Sergei Semenov ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Restriction Pattern ◽  
Type I ◽  
Type Ii ◽  
Genotype I ◽  
Northern Asia ◽  
Hepatitis Delta ◽  
Genotype Ii ◽  
Hdv Genotype ◽  
Delta Virus

Currently, three genotypes of hepatitis delta virus (HDV) are described. The most common, genotype I, has a worldwide distribution; in contrast, genotype II has been found previously only in Japan and Taiwan, while genotype III is found exclusively in South America. Considering the high prevalence of HDV in Northern Siberia (Russia), restriction fragment length polymorphism (RFLP) was used to analyse HDV genotypes from 29 infected patients living in Yakutia. Of these isolates, 11 were characterized by partial nucleotide sequencing and two isolates were completely sequenced. Phylogenetic inference methods included maximum parsimony, maximum likelihood and distance analyses. A restriction pattern consistent with HDV genotype I was found in 14 samples, while the remaining 15 showed a different restriction pattern, inconsistent with any known genotype. Five Yakutian HDV isolates with the type I restriction pattern were sequenced and confirmed to be affiliated with genotype I, although the phylogenetic results indicate that they were heterogeneous and did not cluster together. Sequencing of eight isolates with the new RFLP pattern revealed that these isolates were most closely related to HDV genotype II. In contrast to HDV Yakutian genotype I sequences, all of these type II sequences formed a well-defined clade on phylogenetic trees. Comparison of clinical presentations during hospitalization between patients infected with HDV type I (n=14) and type II (n=15) did not reveal any differences in the severity of infection. These data indicate that the distribution of genotype II is not restricted to Taiwan or Japan, but spreads over Northern Asia, appearing in the native population of Yakutia. Type II Yakutian strains appeared to form a well-defined subclade and could be associated with severe chronic hepatitis in this area.

scholarly journals Current prevalence of hepatitis delta virus (HDV) infection and the range of HDV genotypes in Lebanon

2006 ◽  
Vol 135 (6) ◽  
pp. 959-962 ◽  
Author(s):  
S. RAMIA ◽  
M. EL-ZAATARI ◽  
A. I. SHARARA ◽  
F. RAMLAWI ◽  
B. FARHAT
Keyword(s):  
Hepatitis Delta Virus ◽  
Arab Countries ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Hepatitis D ◽  
Current Prevalence ◽  
Lebanese Population ◽  
Hdv Infection ◽  
Hdv Genotype ◽  
Delta Virus

SUMMARYRecently the prevalence of hepatitis B virus (HBV) genotypes and the association between these genotypes and the clinical status of HBV-infected patients were recently investigated in the Lebanese population. The aim of the additional study reported here was to determine the current prevalence of hepatitis delta virus (HDV) infection and the range of HDV genotypes in this Lebanese population. Two hundred and fifty-eight HBsAg-positive patients (107 asymptomatic blood donors, 92 with chronic hepatitis, 24 with cirrhosis, 15 with hepatocellular carcinoma, 20 patients on haemodialysis) from ten medical centers in Lebanon were tested for antibody to hepatitis D virus (anti-HDV). Those testing positive were analysed further for HDV-RNA and for genotyping by reverse transcriptase–polymerase chain reaction (RT–PCR) and restriction fragment length polymorphism (RFLP). Three samples (1·2%) were anti-HDV positive and out of these, only one was HDV-RNA positive (0·6%) and was analysed as HDV genotype I. Our results point to a low endemicity of HDV in the Lebanese population which is in sharp contrast to data reported from Lebanon 20 years ago and to the situation in neighbouring Arab and non-Arab countries in the Mediterranean region. HDV genotype I seems to be the predominant genotype in Lebanon and the Middle East.

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