scholarly journals High genetic diversity of hepatitis delta virus in eastern Turkey

2014 ◽  
Vol 8 (01) ◽  
pp. 074-078 ◽  
Author(s):  
Yasemin Bulut ◽  
Ibrahim Halil Bahcecioglu ◽  
Cem Aygun ◽  
Pinar Demirel Oner ◽  
Ibrahim Ozercan ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Phylogenetic Analysis ◽  
Restriction Enzyme ◽  
Hepatitis Delta Virus ◽  
Rt Pcr ◽  
Genotype I ◽  
High Genetic Diversity ◽  
Hepatitis Delta ◽  
Hdv Genotype ◽  
Delta Virus

Introduction: Hepatitis delta virus (HDV) is a serious cause of liver-related mortality in patients infected with hepatitis B virus (HBV). Determination of genotypes of HDV and phylogenetic analysis are important for better understanding the pathogenesis of the liver diseases associated with HBV infection. The aim of this study was to determine the genotype or genotypes of HDV among chronically infected patients with HBV in eastern Turkey. Methodology: A group of 113 patients infected with HBV and HDV were included in this study. The samples taken from the patients were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and restriction enzyme cleavage. Results: According to the results of the restriction enzyme analysis, all of the RT-PCR products were determined to be HDV genotype I. Furthermore, for phylogenetic analysis and genotyping, 40 of HDV RT-PCR positive products were sequenced. Phylogenetic analysis of the sequences showed that all of the samples were infected with HDV genotype I. In addition, the results of the alignment analysis showed that the sequences of clinical samples were 82%-95% similar. Conclusion: These results indicate that high genetic diversity of the virus is possible in endemic areas such as Turkey.

scholarly journals Effects of Conserved RNA Secondary Structures on Hepatitis Delta Virus Genotype I RNA Editing, Replication, and Virus Production

2005 ◽  
Vol 79 (17) ◽  
pp. 11187-11193 ◽  
Author(s):  
Geetha C. Jayan ◽  
John L. Casey
Keyword(s):  
Secondary Structure ◽  
Rna Editing ◽  
Hepatitis Delta Virus ◽  
Virus Production ◽  
Rna Replication ◽  
Base Pairing ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Hdv Genotype ◽  
Delta Virus

ABSTRACT RNA editing of the hepatitis delta virus (HDV) antigenome at the amber/W site by the host RNA adenosine deaminase ADAR1 is a critical step in the HDV replication cycle. Editing is required for production of the viral protein hepatitis delta antigen long form (HDAg-L), which is necessary for viral particle production but can inhibit HDV RNA replication. The RNA secondary structural features in ADAR1 substrates are not completely defined, but base pairing in the 20-nucleotide (nt) region 3′ of editing sites is thought to be important. The 25-nt region 3′ of the HDV amber/W site in HDV genotype I RNA consists of a conserved secondary structure that is mostly base paired but also has asymmetric internal loops and single-base bulges. To understand the effect of this 3′ region on the HDV replication cycle, mutations that either increase or decrease base pairing in this region were created and the effects of these changes on amber/W site editing, RNA replication, and virus production were studied. Increased base pairing, particularly in the region 15 to 25 nt 3′ of the editing site, significantly increased editing; disruption of base pairing in this region had little effect. Increased editing resulted in a dramatic inhibition of HDV RNA synthesis, mostly due to excess HDAg-L production. Although virus production at early times was unaffected by this reduced RNA replication, at later times it was significantly reduced. Therefore, it appears that the conserved RNA secondary structure around the HDV genotype I amber/W site has been selected not for the highest editing efficiency but for optimal viral replication and secretion.

scholarly journals A Prenylation Inhibitor Prevents Production of Infectious Hepatitis Delta Virus Particles

2002 ◽  
Vol 76 (20) ◽  
pp. 10465-10472 ◽  
Author(s):  
Bruno B. Bordier ◽  
Patricia L. Marion ◽  
Kazuo Ohashi ◽  
Mark A. Kay ◽  
Harry B. Greenberg ◽  
...  
Keyword(s):  
Hepatitis Delta Virus ◽  
Severe Disease ◽  
Antiviral Agents ◽  
Infectious Hepatitis ◽  
Attractive Potential ◽  
Farnesyltransferase Inhibitors ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Hdv Genotype ◽  
Delta Virus

ABSTRACT Hepatitis delta virus (HDV) causes both acute and chronic liver disease throughout the world. Effective medical therapy is lacking. Previous work has shown that the assembly of HDV virus-like particles (VLPs) could be abolished by BZA-5B, a compound with farnesyltransferase inhibitory activity. Here we show that FTI-277, another farnesyltransferase inhibitor, prevented the production of complete, infectious HDV virions of two different genotypes. Thus, in spite of the added complexity and assembly determinants of infectious HDV virions compared to VLPs, the former are also sensitive to pharmacological prenylation inhibition. Moreover, production of HDV genotype III virions, which is associated with particularly severe clinical disease, was as sensitive to prenylation inhibition as was that of HDV genotype I virions. Farnesyltransferase inhibitors thus represent an attractive potential class of novel antiviral agents for use against HDV, including the genotypes associated with most severe disease.

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.

scholarly journals Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease

2003 ◽  
Vol 84 (12) ◽  
pp. 3275-3289 ◽  
Author(s):  
Hideki Watanabe ◽  
Kazuyoshi Nagayama ◽  
Nobuyuki Enomoto ◽  
Ryoko Chinzei ◽  
Tsuyoshi Yamashiro ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis Delta Virus ◽  
Phylogenetic Tree Analysis ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Hepatitis Delta Virus Infection ◽  
Significant Difference ◽  
Genetic Subgroup ◽  
Hdv Genotype ◽  
Delta Virus

We determined the sequence of the hepatitis delta virus (HDV) genome in 40 Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan. Consensus sequences from 33 HDV full genomes out of a total of 40 patients were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I (two patients), genotype IIa (one patient) and genotype IIb (30 patients). Among the 30 genotype IIb patients, there were two clusters of genetic variants. One group consisted of six isolates showing significant homology with genotype IIb, previously reported from Taiwan. The other group consisted of 24 isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb-M). When the genetic structures were compared in detail between IIb and IIb-M, characteristic variations were found in the C-terminal sequence of the large delta antigen-conferring packaging signal as well as the RNA editing site. Determination of subclasses of genotype IIb in a total of 37 patients, including seven HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Although there was no significant difference in the clinical background or virological state of hepatitis B virus between these two groups, patients with genotype IIb-M showed greater progression of chronic hepatitis and cirrhosis than those with genotype IIb (P=0·0009). These data indicate the existence of a genetic subgroup of HDV genotype IIb, which is associated with different clinical characteristics and which could be related to genetic variations in functionally important parts of the HDV genome.

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 Genetic Changes in Hepatitis Delta Virus from Acutely and Chronically Infected Woodchucks

2006 ◽  
Vol 80 (13) ◽  
pp. 6469-6477 ◽  
Author(s):  
John L. Casey ◽  
Bud C. Tennant ◽  
John L. Gerin
Keyword(s):  
Hepatitis Delta Virus ◽  
Hepatitis Virus ◽  
Consensus Sequence ◽  
Genotype I ◽  
Hepatitis Delta ◽  
Genetic Changes ◽  
Host Immune Responses ◽  
Hepatitis Delta Antigen ◽  
Hdv Infection ◽  
Delta Virus

ABSTRACT A woodchuck-derived hepatitis delta virus (HDV) inoculum was created by transfection of a genotype I HDV cDNA clone directly into the liver of a woodchuck that was chronically infected with woodchuck hepatitis virus. All woodchucks receiving this inoculum became positive for HDV RNA in serum, and 67% became chronically infected, similar to the rate of chronic HDV infection in humans. Analysis of HDV sequences obtained at 73 weeks postinfection indicated that changes had occurred at a rate of 0.5% per year; many of these modifications were consistent with editing by host RNA adenosine deaminase. The appearance of sequence changes, which were not evenly distributed on the genome, was correlated with the course of HDV infection. A limited number of modifications occurred in the consensus sequence of the viral genome that altered the sequence of the hepatitis delta antigen (HDAg). All chronically infected animals examined exhibited these changes 73 weeks following infection, but at earlier times, only one of the HDV carriers exhibited consensus sequence substitutions. On the other hand, sequence modifications in animals that eventually recovered from HDV infection were apparent after 27 weeks. The data are consistent with a model in which HDV sequence changes are selected by host immune responses. Chronic HDV infection in woodchucks may result from a delayed and weak immune response that is limited to a small number of epitopes on HDAg.

scholarly journals Endemicity And Genetic Diversity of Hepatitis Delta Virus Among Pygmies In Cameroon, Central Africa.

2021 ◽  
Author(s):  
Yacouba Foupouapouognigni ◽  
Jacques Delors Mfonkou Toumansie ◽  
Onana Boyomo ◽  
Antoine Gessain ◽  
Richard Njouom
Keyword(s):  
Genetic Diversity ◽  
Hepatitis Delta Virus ◽  
Phylogenetic Analyses ◽  
Central Africa ◽  
African Origin ◽  
Hepatitis Delta ◽  
Chronic Hbv ◽  
Hdv Infection ◽  
Very High ◽  
Delta Virus

Abstract A single study conducted two decades ago on hepatitis delta virus (HDV) infections among Baka Pygmies in Cameroon reported a very high antibody prevalence of 46%, but HDV genetic diversity has not yet been studied in this remote population. In the present study, we investigated the HDV seroprevalence and the genotype diversity in the three main Cameroonian Pygmy populations with chronic HBV infection. An unusually high (69.2%) level of HDV infection was found among HBsAg-positive Pygmies in Cameroon. Phylogenetic analyses showed the co-circulation of highly diverse HDV genotypes HDV-1 and HDV-7 in this population. These results highlighted the endemicity of HDV infection in Central Africa and suggest an african origin of HDV.

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