Nucleotide sequences of the hepatitis C virus core region in patients without anti-core antibody

Nagasaka, Atsushi; Hige, Shuhei; Kurosawa, Mitsutoshi; Yoshida, Jun‐ichi; Karino, Yoshiyasu; Toyota, Jouji; Mizutani, Takashi; Asaka, Masahiro

doi:10.1002/(sici)1096-9071(199606)49:2<91::aid-jmv4>3.0.co;2-e

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…Two amino acid changes T.A at aa75 and S.N at aa106 were found. However, similar substitutions have already been reported that were not associated with the absence of anti-core antibodies [38].…”

Section: Analysis Of the Core Region Of Hcv Isolates Derived From The...supporting

confidence: 84%

Correction: Synonymous Mutations in the Core Gene Are Linked to Unusual Serological Profile in Hepatitis C Virus Infection

Agata¹,

Kakkanas²,

Eric³

et al. 2011

PLoS ONE

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The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T.C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of antit-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection.

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Section: Analysis Of the Core Region Of Hcv Isolates Derived From The...supporting

confidence: 84%

Correction: Synonymous Mutations in the Core Gene Are Linked to Unusual Serological Profile in Hepatitis C Virus Infection

Agata¹,

Kakkanas²,

Eric³

et al. 2011

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…It is interesting that C100 and NS5 antigens were significantly less recognized by the low-responder sera in this study (Table 3). However, other studies have shown that the absence of reactivity to the core and other regions is not always attributable to variability in the infecting HCV strain (7,13), suggesting that the genetic constitution of the host may also play a role in restricting recognition of these viral antigens, especially when synthetic peptides are used. In this particular cohort of hemodialysis patients, all the common genotypes circulating among different Venezuelan groups (1a, 1b, 2a, and 3a), except genotype 2b, were found (18), and no difference was found in genotype distribution among the lowresponder patients compared to the high responders.…”

Section: Discussionmentioning

confidence: 99%

Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus

Devesa

Khudyakov

Capriles

et al. 1997

Clin Diagn Lab Immunol

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Antibody reactivities to hepatitis C virus (HCV) antigens and to synthetic peptides derived from different parts of the HCV genome (core, NS4, and NS5) were evaluated in HCV-infected hemodialysis patients. In the RIBA 3 assay, NS5 was significantly less recognizable by sera of hemodialysis patients compared to other HCV-infected subjects. Among hemodialysis patients, those coinfected with hepatitis B virus (HBV) (positive for hepatitis B surface antigen [HBsAg ؉ ]) showed a reduction in reactivity to C33 and C100. Sera of only 23% of the hemodialysis patients (37 of 161) reacted with more than three of eight peptides tested, significantly fewer than the 60% (12 of 20) of the sera of other HCV-infected patients tested (P ‫؍‬ 0.001). This immunosuppression was also manifested by a reduced frequency of recognition of additional peptides on follow-up. An even more reduced reactivity was observed among the HBV-coinfected patients (HBsAg ؉). The low-responder hemodialysis patients were not infected with any particular genotype of HCV, and the same HCV genotypes observed in the whole group of hemodialysis patients (1a, 1b, 2a, and 3a) were found circulating in the low-responder group. Even in this low-responder population, the good performance of two peptides (peptide 716, corresponding to a portion of the core, and peptide 59, corresponding to a portion of NS4) corroborates the immunodominance of the conserved epitopes within these peptides.

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HCV core immunodominant region analysis using mouse monoclonal antibodies and human sera: Characterization of major epitopes useful for antigen detection

et al. 1998

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Monoclonal antibodies (MAbs) were generated by immunizing mice with a truncated recombinant protein corresponding to the immunodominant region (residues 1-120) of hepatitis C virus (HCV) nucleocapsid protein. The specific recognition by either human sera or mouse monoclonal antibodies of overlapping peptides spanning the core region 1-120 as well as the comparison with epitopes described earlier allowed the fine mapping of HCV core. Within the region 1-120, the major antigenic domain could be restricted to the first 45 amino acids. Indeed, the peptide S42G (residues 2-45) allowed the detection of an anti-HCV core response by all anticore-positive human sera examined. According to their epitope localization, three groups of mouse MABs could be evidenced that were directed against different regions of core. Group II MAbs recognized a strictly linear epitope (QDVKF, residues 20-24), whereas group I MABs were directed against a conformational epitope mainly located at the amino acid residues (QIVGG, 29-33). The epitope of group III MABs was also conformational (PRGRRQPI, residues 58-65). These three epitopes appeared close but different from the three major human epitopes RKTKRNTN, VYLLPR, and GRTWAQPGYPWPLY (residues 7-17, 34-39, and 73-86, respectively). Group II MAB 7G12A8 and group I MAB 19D9D6 were used in a sandwich ELISA for the capture and the detection, respectively, of viral core antigen in sera of patients with chronic HCV infection. After treatment of sera with triton x 100 in acidic conditions, amounts of viral antigen as low as 20 pg/ml of sera could be detected.

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Nucleotide sequences of the hepatitis C virus core region in patients without anti-core antibody

Cited by 8 publications

References 17 publications

Correction: Synonymous Mutations in the Core Gene Are Linked to Unusual Serological Profile in Hepatitis C Virus Infection

Correction: Synonymous Mutations in the Core Gene Are Linked to Unusual Serological Profile in Hepatitis C Virus Infection

Reduced antibody reactivity to hepatitis C virus antigens in hemodialysis patients coinfected with hepatitis B virus

HCV core immunodominant region analysis using mouse monoclonal antibodies and human sera: Characterization of major epitopes useful for antigen detection

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