Characterization of a Linear Epitope in the Nonstructural Region 4 of Hepatitis C Virus with Reactivity to Seroconversion Antibodies

Wienhues, Ulla; Ihlenfeldt, Hans-Georg; Seidel, Christoph; Schmitt, Urban; Kraas, Wolfgang; Jung, Günther

doi:10.1006/viro.1998.9163

Cited by 8 publications

(3 citation statements)

References 20 publications

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“…This suggests more variation in immuno-genic core and NS4 B-cell epitopes relative to NS3 and NS5. To confirm that immunodominant epitopes, previously published by others, [27][28][29][30][31][32][33][34] were indeed type-specific in all four proteins used in the Chiron RIBA HCV titering SIA, we performed amino acid alignments of all four proteins for different HCV genotypes. The short synthetic peptides of the core and NS4 region used in the assay show, especially in NS4, significant epitope variability between different genotypes.…”

Section: Relationship Between Hcv-specific Antibody Responses and Hcvmentioning

confidence: 76%

Quantitative antibody responses to structural (core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: Impact of epitope variation and relationship to detection of HCV RNA in blood

et al. 1999

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To gain insight into the natural history of hepatitis C virus (HCV), 13 human immunodeficiency virus (HIV)-seronegative injecting drug users were studied who seroconverted for HCV as determined by third-generation enzymelinked immunosorbent assay, showed an ensuing antibody response to HCV, and were not treated with any antiviral drugs during follow-up. Subjects included 13 untreated HIV-negative individuals, of whom 5 (38.5%) apparently cleared HCV and were polymerase chain reaction (PCR)-negative in at least 3 consecutive samples, 3 (23.1%) showed transient viremia and were PCR-negative in 1 sample during the study period, and the other 5 (38.5%) showed persistent viremia. Viremia was determined longitudinally by reverse-transcription PCR (RT-PCR) and quantified by branched DNA (bDNA). HCV genotypes were determined on serial samples during follow-up. Quantitative antibody levels to core, NS3, NS4, and NS5 were determined using the Chiron RIBA HCV-titering Strip Immunoblot Assay, which is based on HCV genotype 1. The antibody responses to core, NS3, NS4, and NS5 were erratic. In individuals infected with HCV genotype 1, significantly higher median antibody responses to core (P ‫؍‬ .02) and to NS4 (P ‫؍‬ .04) were found as compared with those infected with other genotypes, showing a significant impact of HCV genotype specificity of the assay. In groups infected with HCV genotype 1, significantly higher median

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Section: Relationship Between Hcv-specific Antibody Responses and Hcvmentioning

confidence: 76%

Quantitative antibody responses to structural (core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: Impact of epitope variation and relationship to detection of HCV RNA in blood

et al. 1999

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“…The 20-mer peptide derived from NS4 (peptide 59) and included in the cocktail contains a sequence highly conserved among different HCV isolates, which might be one of the reasons for its high frequency of recognition (5,10,11). Antibodies against peptide 59 seem to be raised at early stages of infection, with some degree of antigenic cross-reactivity with proteins from different origins (24). In our study, the use of peptide 59 in the cocktail did not produce nonspecific reactions.…”

mentioning

confidence: 53%

Restricted Isotypic Antibody Reactivity to Hepatitis C Virus Synthetic Peptides in Immunocompromised Patients

Devesa¹,

Saez²,

León³

et al. 1999

Clin Diagn Lab Immunol

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“…The strategy of excluding nonspecific epitopes from the design of an artificial protein was used to construct the hepatitis E mosaic antigen [Khudyakov et al, 1994]. Recently, nonspecific immunoreactivity was detected with synthetic peptides derived from region 59 [Wienhues et al, 1998]. Because the NS4 mosaic protein was constructed before this publication, sequences associated with this nonspecific immunoreactivity were included in the artificial NS4 mosaic protein.…”

Section: Discussionmentioning

confidence: 99%

Artificial NS4 mosaic antigen of hepatitis C virus

et al. 1999

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An artificial antigen composed of 17 small antigenic regions derived from the NS4-protein of hepatitis C virus (HCV) genotypes 1 through 5 was designed and constructed. Eleven antigenic regions were derived from the 5-1-1 region, and 6 others were derived from the C-terminus of the NS4-protein of different genotypes. The gene encoding for this artificial antigen was assembled from synthetic oligonucleotides by a new approach designated as restriction enzyme-assisted ligation (REAL). The full-length synthetic gene was expressed in Escherichia coli as a fusion protein with glutathione S-transferase. By the use of site-specific antibodies raised against synthetic peptides, it was shown that all regions for which sequence-specific antibodies were obtained were accessible to antibody binding. The diagnostic relevance of the NS4 artificial antigen was demonstrated by testing this antigen with 4 HCV seroconversion panels and a panel of previously tested and stored serum specimens. The artificial antigen was found to specifically detect anti-NS4 antibodies in a number of specimens that were previously found to be anti-NS4 negative. Furthermore, this antigen detected anti-NS4 activity earlier in 2 of 4 seroconversion panels than did the antigen used in a commercially available supplemental assay. Equally important is the observation that the artificial NS4 antigen demonstrated equivalent anti-NS4 immunoreactivity with serum specimens obtained from patients infected with different HCV genotypes, whereas the NS4 recombinant protein derived from genotype 1, used in the commercial supplemental test, was less immunoreactive with serum specimens containing HCV genotypes 2, 3, and 4. Collectively, these data support the significant diagnostic potential of the NS4 mosaic antigen. The strategy employed in this study may be applied to the design and construction of other artificial antigens with improved diagnostically pertinent properties. J. Med. Virol. 59:437-450 1999.

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Characterization of a Linear Epitope in the Nonstructural Region 4 of Hepatitis C Virus with Reactivity to Seroconversion Antibodies

Cited by 8 publications

References 20 publications

Quantitative antibody responses to structural (core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: Impact of epitope variation and relationship to detection of HCV RNA in blood

Quantitative antibody responses to structural (core) and nonstructural (NS3, NS4, and NS5) hepatitis C virus proteins among seroconverting injecting drug users: Impact of epitope variation and relationship to detection of HCV RNA in blood

Restricted Isotypic Antibody Reactivity to Hepatitis C Virus Synthetic Peptides in Immunocompromised Patients

Artificial NS4 mosaic antigen of hepatitis C virus

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