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 ◽  
...  

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.

2005 ◽  
Vol 79 (17) ◽  
pp. 11187-11193 ◽  
Author(s):  
Geetha C. Jayan ◽  
John L. Casey

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.


2013 ◽  
Vol 144 (5) ◽  
pp. S-450
Author(s):  
Liana S. Gheorghe ◽  
Irma Csiki ◽  
Speranta Iacob ◽  
Anca Trifan ◽  
Mircea D. Grigorescu ◽  
...  

2008 ◽  
Vol 10 (5) ◽  
pp. 291-301 ◽  
Author(s):  
U. Schlipköter ◽  
A. Ponzetto ◽  
K. Fuchs ◽  
R. Rasshofer ◽  
S. S. Choi ◽  
...  

2014 ◽  
Vol 8 (01) ◽  
pp. 074-078 ◽  
Author(s):  
Yasemin Bulut ◽  
Ibrahim Halil Bahcecioglu ◽  
Cem Aygun ◽  
Pinar Demirel Oner ◽  
Ibrahim Ozercan ◽  
...  

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.


2002 ◽  
Vol 76 (20) ◽  
pp. 10465-10472 ◽  
Author(s):  
Bruno B. Bordier ◽  
Patricia L. Marion ◽  
Kazuo Ohashi ◽  
Mark A. Kay ◽  
Harry B. Greenberg ◽  
...  

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.


2001 ◽  
Vol 82 (11) ◽  
pp. 2709-2718 ◽  
Author(s):  
Valeria Ivaniushina ◽  
Nadjia Radjef ◽  
Marfa Alexeeva ◽  
Elyanne Gault ◽  
Sergei Semenov ◽  
...  

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.


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