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Hepatitis D Virus: A Call to Screening.

ABSTRACT: Hepatitis D virus causes an aggressive viral hepatitis with a virulent course of progression to cirrhosis and hepatic decompensation. It relies on hepatitis B coinfection for its pathogenesis and propagation. Hepatitis D virus had become the forgotten virus, with reduced public awareness, medical interest, and research support. Recently, there has been a resurgence of awareness and interest in hepatitis D, with improvements in diagnostic testing and establishment of international collaborative efforts to improve therapy. This article provides a framework to understand the impetus for increased screening as well as to identify key issues toward which collaborative efforts can be directed.

SUBMITTER: Ahn J

PROVIDER: S-EPMC4988222 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Hepatitis D Virus: A Call to Screening.

Ahn Joseph J Gish Robert G RG

Gastroenterology & hepatology 20141001 10

Hepatitis D virus causes an aggressive viral hepatitis with a virulent course of progression to cirrhosis and hepatic decompensation. It relies on hepatitis B coinfection for its pathogenesis and propagation. Hepatitis D virus had become the forgotten virus, with reduced public awareness, medical interest, and research support. Recently, there has been a resurgence of awareness and interest in hepatitis D, with improvements in diagnostic testing and establishment of international collaborative e ...[more]

PMID: 27540336

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Project description:BACKGROUND: The National Institutes of Health classified Hepatitis E as an emerging disease since Hepatitis E Virus (HEV) is the major cause of acute hepatitis in developing countries. Interestingly, an increasing number of sporadic cases of HEV infections are described in industrialized countries as zoonosis from domestic livestock. Despite the increasing relevance of this pathogen in clinical virology, commercial antibody assays are mainly based on fragments of HEV open reading frame (ORF) 2 and ORF3. The largest ORF1 (poly-)protein, however, is not part of current testing formats. METHODS: From a synthesized full length HEV genotype 1 cDNA-bank we constructed a complete HEV gene library consisting of 15 respective HEV ORF domains. After bacterial expression and purification of nine recombinant HEV proteins under denaturating conditions serum profiling experiments using 55 sera from patients with known infection status were performed in microarray format. SPSS software assessed the antigenic potential of these nine ORF domains in comparison to seven commercial HEV antigens (genotype 1 and 3) by performing receiver operator characteristics, logistic regression and correlation analysis. RESULTS: HEV antigens produced with our method for serum profiling experiments exhibit the same quality and characteristics as commercial antigens. Serum profiling experiments detected Y, V and X domains as ORF1-antigens with potentially comparable diagnostic significance as the well established epitopes of ORF2 and ORF3. However no obvious additional increase in sensitivity or specificity was achieved in diagnostic testing as revealed by bioinformatic analysis. Additionally we found that the C-terminal domain of the potential transmembrane protein ORF3 is responsible for IgG and IgM seroreactivity. Data suggest that there might be a genotype specific seroreactivity of homologous ORF2-antigens. CONCLUSIONS: The diagnostic value of identified ORF1 epitopes might not necessarily improve sensitivity and specificity, but broaden the overall quality of existing test systems. ORF2 and ORF3-antigens are still commonly used in diagnostic assays and possibly hold the potential to serologically differentiate between genotype 1 and 3 infections. Our systematic approach is a suitable method to investigate HEV domains for their serologic antigenicity. Epitope screening of native viral domains could be a preferable tool in developing new serologic test components.

Dataset Information

Hepatitis D Virus: A Call to Screening.

Publications

Hepatitis D Virus: A Call to Screening.

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