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Journal of Virology, October 2004, p. 10460-10469, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10460-10469.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Memory T-Cell-Mediated Immune Responses Specific to an Alternative Core Protein in Hepatitis C Virus Infection

Christine Bain,1,{dagger} Peggy Parroche,1,{dagger} Jean Pierre Lavergne,2 Blandine Duverger,3 Claude Vieux,4 Valérie Dubois,5 Florence Komurian-Pradel,3 Christian Trépo,4 Lucette Gebuhrer,5 Glaucia Paranhos-Baccala,3 François Penin,2 and Geneviève Inchauspé1*

FRE 2736, Ecole Normale Supérieure,1 Laboratoire de Bioinformatique et RMN structurales, Institut de Biologie et chimie des protéines, UMR 5086 CNRS, Université Claude Bernard Lyon I,2 UMR 2714, Tour CERVI, IFR 128 Biosciences Lyon Gerland,3 Hôtel Dieu,4 Etablissement de Transfusion Sanguine, Lyon, France5

Received 4 February 2004/ Accepted 27 May 2004

In vitro studies have described the synthesis of an alternative reading frame form of the hepatitis C virus (HCV) core protein that was named F protein or ARFP (alternative reading frame protein) and includes a domain coded by the +1 open reading frame of the RNA core coding region. The expression of this protein in HCV-infected patients remains controversial. We have analyzed peripheral blood from 47 chronically or previously HCV-infected patients for the presence of T lymphocytes and antibodies specific to the ARFP. Anti-ARFP antibodies were detected in 41.6% of the patients infected with various HCV genotypes. Using a specific ARFP 99-amino-acid polypeptide as well as four ARFP predicted class I-restricted 9-mer peptides, we show that 20% of the patients display specific lymphocytes capable of producing gamma interferon, interleukin-10, or both cytokines. Patients harboring three different viral genotypes (1a, 1b, and 3) carried T lymphocytes reactive to genotype 1b-derived peptides. In longitudinal analysis of patients receiving therapy, both core and ARFP-specific T-cell- and B-cell-mediated responses were documented. The magnitude and kinetics of the HCV antigen-specific responses differed and were not linked with viremia or therapy outcome. These observations provide strong and new arguments in favor of the synthesis, during natural HCV infection, of an ARFP derived from the core sequence. Moreover, the present data provide the first demonstration of the presence of T-cell-mediated immune responses directed to this novel HCV antigen.

* Corresponding author. Mailing address: UMR 2142, Ecole Normale Supérieure de Lyon, 46, allée d'Italie, 69364 LYON Cedex 07, France. Phone: 33 4 72 72 85 90. Fax: 33 4 72 72 85 33. E-mail: genevieve.inchauspe{at}ens-lyon.fr.

{dagger} C.B. and P.P. contributed equally.

Journal of Virology, October 2004, p. 10460-10469, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10460-10469.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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