scholarly journals Positive Selection of Hepatitis Delta Antigen in Chronic Hepatitis D Patients

2007 ◽  
Vol 81 (9) ◽  
pp. 4438-4444 ◽  
Author(s):  
Shen-Yung Wang ◽  
Jaw-Ching Wu ◽  
Tzen-Yuh Chiang ◽  
Yi-Hsiang Huang ◽  
Chien-Wei Su ◽  
...  

ABSTRACT Liver disease may become ameliorated in some patients with chronic hepatitis D virus (HDV) infection. We present here a study based on longitudinal sampling to investigate the viral dynamics in chronic HDV infection. We examined the HDV variants from different time points, especially those before and after the elevation of serum aminotransferase levels. The datasets from each patient were tested for positive selection by using maximum-likelihood methods with heterogeneous selective pressures along the nucleotide sequence. An average of 4.9%, ranging from 3.1 to 6.8%, of the entire delta antigen sites was regulated by a diversifying selection. Most of the positively selected sites were associated with immunogenic domains. Likelihood ratio tests revealed a significant fitness of positive selection over neutrality of the hepatitis delta antigen gene in all patients. We further adapted a neural network method to predict potential cytotoxic T ligand epitopes. Among the HLA-A*0201 cytotoxic T ligand epitopes, three consistent epitopes across all three genotypes were identified: amino acids (aa) 43 to 51, 50 to 58, and 114 to 122. Three patients (60%) had sites evolving under positive selection in the epitope from aa 43 to 51, and four patients (80%) had sites evolving under positive selection in the epitope from aa 114 to 122. The discovery of immunogenic epitopes, especially cytotoxic-T-lymphocyte ligands, associated with chronic HDV infection may be crucial for further development of novel treatments or designs in vaccine for HDV superinfection.

2012 ◽  
Vol 19 (5) ◽  
pp. 817-819 ◽  
Author(s):  
Yung-Bin Kuo ◽  
Mei Chao ◽  
Yi-Hsuan Lee ◽  
Chau-Ting Yeh ◽  
Err-Cheng Chan

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.


2004 ◽  
Vol 78 (6) ◽  
pp. 2693-2700 ◽  
Author(s):  
Sheng-Chieh Hsu ◽  
Jaw-Ching Wu ◽  
I-Jane Sheen ◽  
Wan-Jr Syu

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.


2021 ◽  
Vol 2 (2) ◽  
pp. 19-26
Author(s):  
Adela TURCANU ◽  
Suhaib TAHIR WANI

Introduction. Hepatitis delta virus (HDV) is a small, defective RNA virus that is related more to plant viroids than to other human pathogens. Material and methods. Nearly 50 research articles from various sources were reviewed and a comprehensive analysis was done regarding various parameters concerning HDV. Articles published over a period of 30 years were selected based on their experimental and statistical relevance to HDV. This review gives a brief insight into epidemiology, genetics, clinical evolution and treatment of chronic hepatitis delta. Results. Chronic hepatitis delta remains a major cause of morbidity in Eastern European countries and the Mediterranean region. At the same time, there is a resurgence of HBV and HDV infection in young people (under the age of 50) in Western Europe, as a consequence of the intra-familial and sexual mode of acquisition among immigrants from Eastern Europe, the Mediterranean region and from countries of the former Soviet Union, Africa high burdened regions of Asia and South America. Prevalence among IVDU was found to be higher especially in western european countries and other regions of low HDV prevalence. Chronic delta viral hepatitis is a dynamic, progressive process. A direct cytopathic pattern of liver tissue damage was also observed, especially in the presence of HDV genotype 3. Chronic hepatitis D is reported to progress to cirrhosis and hepatocellular cancer, and this trend is greater the higher the level of HDV viremia at the time of presentation. Conclusions. Flaws in screening and on-time diagnosis still remain due to the insufficient research and data available. While still not classified as a carcinogen by IARC, our review ends up in support of the notion that HDV infection increases the chances and fastens the pathogenic processes leading to HCC.


2002 ◽  
Vol 83 (10) ◽  
pp. 2507-2513 ◽  
Author(s):  
Gwo-Tarng Sheu

The hepatitis delta virus (HDV) nucleocapsid consists of a genomic-length RNA of 1·7 kb and approximately equimolar amounts of the small and large forms of the hepatitis delta antigen (S-HDAg and L-HDAg, respectively). Since HDV RNA particles contain not only a genomic RNA species encoding S-HDAg but also an RNA species encoding L-HDAg, which is produced by an RNA-editing process, the question arises as to whether RNAs encoding either L-HDAg or S-HDAg can initiate replication. To study this, two cDNA-free transfection methods were employed: HDV RNA cotransfected with either the S-HDAg-encoding mRNA species or the ribonucleocapsid protein complex, comprising HDV RNA and recombinant S-HDAg. Results showed that the genomic-sense RNA encoding S-HDAg could promote HDV replication, whereas the L-HDAg-encoding RNA species was unable to replicate under the same conditions. The antigenomic RNA species encoding either S-HDAg or L-HDAg could not replicate by either of these procedures. In addition, L-HDAg alone could not promote replication of the genomic RNA but, by supplementing an equal amount of S-HDAg, replication occurred. These data indicate that L-HDAg-encoding RNA species are probably not involved in the initiation of HDV RNA synthesis; instead, their main function may be to serve as template for producing L-HDAg, which regulates HDV RNA synthesis and virion assembly. These results suggest that the genomic RNA species encoding S-HDAg is the only functional genome for HDV infection and explain why the presence of the edited HDV RNA encoding L-HDAg does not interfere with HDV infection.


1988 ◽  
Vol 158 (1) ◽  
pp. 151-159 ◽  
Author(s):  
F. Negro ◽  
K. F. Bergmann ◽  
B. M. Baroudy ◽  
W. C. Satterfield ◽  
H. Popper ◽  
...  

2000 ◽  
Vol 275 (48) ◽  
pp. 37311-37316 ◽  
Author(s):  
Tadashi Goto ◽  
Naoya Kato ◽  
Suzane Kioko Ono-Nita ◽  
Hideo Yoshida ◽  
Motoyuki Otsuka ◽  
...  

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