Demonstration of a hepatitis C virus-specific antigen predicted from the putative core gene in the circulation of infected hosts

Takahashi, Kazuaki; Okamoto, Hiroaki; Kishimoto, Seiji; Munekata, Eisuke; Tachibana, K; Akahane, Yoshihiro; Yamada, Hiroshi; Mishiro, Shunji

doi:10.1099/0022-1317-73-3-667

Cited by 55 publications

(32 citation statements)

References 14 publications

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“…The principles of assays used in this study for detection of HCV core are different from those of all other assays published before (1,19,32,33,(38)(39)(40) or recently commercialized (Ortho Diagnostics), which use detergents or denaturing agents for pretreatment of serum samples or in a "sample diluent." These assays mainly quantify the core protein from denatured HCV virions.…”

Section: Discussionmentioning

confidence: 99%

“…This may be due to the low concentration of circulating virions, their association with lipoproteins and/or antibodies, or the inability of the available monoclonal antibodies (MAbs) to recognize HCV particles. HCV core protein is the only HCV antigen detected by immunological methods, after the treatment of serum samples by detergents or denaturing agents, which remove the envelope of the virion and expose its internal component (1,19,32,38,39). Such assays have proved useful for the detection of core antigen in the sera of HCV patients (19,32,40), especially in the antibody-negative early phase of HCV-related liver disease (33).…”

mentioning

confidence: 99%

“…Core protein maps to the N-terminal 191 aa residues of the HCV polyprotein, and its primary function is formation of the viral nucleocapsid (38,39). The sites of interaction with homologous and heterologous RNA have been mapped to the N-terminal region of the HCV core protein, whereas the main homotypic interaction domain maps to the tryptophan-rich sequence (aa 73 to 108) (30).…”

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confidence: 99%

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Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients

Maillard¹,

Krawczyński

Nitkiewicz³

et al. 2001

J Virol

168

133

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One of the characteristics of hepatitis C virus (HCV) is the high incidence of persistent infection. HCV core protein, in addition to forming the viral nucleocapsid, has multiple regulatory functions in host-cell transcription, apoptosis, cell transformation, and lipid metabolism and may play a role in suppressing host immune response. This protein is thought to be present in the bloodstream of the infected host as the nucleocapsid of infectious, enveloped virions. This study provides evidence that viral particles with the physicochemical, morphological, and antigenic properties of nonenveloped HCV nucleocapsids are present in the plasma of HCV-infected individuals. These particles have a buoyant density of 1.32 to 1.34 g/ml in CsCl, are heterogeneous in size (with predominance of particles 38 to 43 or 54 to 62 nm in diameter on electron microscopy), and express on their surface epitopes located in amino acids 24 to 68 of the core protein. Similar nucleocapsid-like particles are also produced in insect cells infected with recombinant baculovirus bearing cDNA for structural HCV proteins. HCV core particles isolated from plasma were used to generate anti-core monoclonal antibodies (MAbs). These MAbs stained HCV core in the cytoplasm of hepatocytes from experimentally infected chimpanzees in the acute phase of the infection. These chimpanzees had concomitantly HCV core antigen in serum. These findings suggest that overproduction of nonenveloped nucleocapsids and their release into the bloodstream are properties of HCV morphogenesis. The presence of circulating cores in serum and accumulation of the core protein in liver cells during the early phase of infection may contribute to the persistence of HCV and its many immunopathological effects in the infected host.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients

Maillard¹,

Krawczyński

Nitkiewicz³

et al. 2001

J Virol

168

133

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“…Thus HCV is suggested to be relatively fragile. Also noteworthy is the possible influence of density media on the estimated value of the buoyant density of HCV; it was 1.11 g/ml in potassium bromide (Takahashi et al, 1992).…”

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confidence: 99%

Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction

Miyamoto

Okamoto

Sato

et al. 1992

Journal of General Virology

Self Cite

102

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“…Although the PCR assay is very sensitive in detecting the serum HCV RNA, the results sometimes have problems of specificity and precision, and blind comparisons have significant error rates (37). Methods for detecting viral antigens (Ag) were developed by applying a monoclonal antibody to the HCV core Ag (19,33,35); however, the assays have been insufficient for clinical application because of their low sensitivity and the requirement for complicated specimen pretreatment. An accurate and specific new HCV core Ag detection assay system (total HCV core Ag assay) (2) has recently been developed and is commercially available in European countries (trak-C assay) (7,20,24,25,31); it has a lower detection level limit of 1.5 pg/ml, which is equivalent to 20 KIU/ml.…”

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confidence: 99%

Benefit of Hepatitis C Virus Core Antigen Assay in Prediction of Therapeutic Response to Interferon and Ribavirin Combination Therapy

et al. 2005

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A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity ‫؍‬ 100%, specificity ‫؍‬ 85.0%, accuracy ‫؍‬ 86.4%), whereas RNA negativity could predict SVR on day 7 (sensitivity ‫؍‬ 100%, specificity ‫؍‬ 87.2%, accuracy ‫؍‬ 88.6%). None of the patients who had detectable serum core Ag or RNA on day 14 achieved SVR (specificity ‫؍‬ 100%). The predictive accuracy on day 14 was higher by RNA negativity (93.2%) than that by core Ag negativity (75.0%). The combined predictive criterion of both viral load decline during the first 24 h and basal viral load was also predictive for SVR; the sensitivities of Lumipulse-Ag and Amplicor-M were 45.5 and 47.6%, respectively, and the specificity was 100%. Amplicor-M had better predictive accuracy than Lumipulse-Ag in 2-week disappearance tests because it had better sensitivity. On the other hand, estimates of kinetic parameters were similar regardless of the detection method. Although the correlations between Lumipulse-Ag and Amplicor-M were good both before and 24 h after IFN administration, HCV core Ag seemed to be relatively lower 24 h after IFN administration than before administration. Lumipulse-Ag seems to be useful for detecting the HCV concentration during IFN therapy; however, we still need to understand the characteristics of the assay.Hepatitis C virus (HCV) infection causes a slowly progressive disease which can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (28, 30). Successful interferon (IFN) therapy for HCV leads to persistently undetectable serum viral levels and histological improvement (9, 11) and improves the survival of chronic hepatitis C patients by preventing liver-related deaths (36). A meta-analysis study including data from randomized trials showed that retreatment of nonresponders with a combination of IFN-␣2b and ribavirin (RBV) for 24 weeks was associated with only 14% sustained virological response (SVR) in genotype 1-infected patients (4). When a combination of pegylated interferon (IFN) and RBV was used as retreatment for 48 weeks, a 46% SVR rate was reached; however, patients infected with genotype 1 still had a limited chance of achieving SVR (12).Studies aimed at understanding the predictive value of SVR and non-SVR in the absence or presence of serum RNA during IFN therapy within 2 days (32), 1 week (18), 2 weeks (17), 1 month (3,6,13,15,29,39), or 3 months (23) have been reported. The biphasic or triphasic initial decline in the level of serum HCV RNA after IFN therapy has also been characterized and analyzed m...

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Demonstration of a hepatitis C virus-specific antigen predicted from the putative core gene in the circulation of infected hosts

Cited by 55 publications

References 14 publications

Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients

Nonenveloped Nucleocapsids of Hepatitis C Virus in the Serum of Infected Patients

Extraordinarily low density of hepatitis C virus estimated by sucrose density gradient centrifugation and the polymerase chain reaction

Benefit of Hepatitis C Virus Core Antigen Assay in Prediction of Therapeutic Response to Interferon and Ribavirin Combination Therapy

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