Memory T-cell-mediated immune responses specific to an alternative core protein in hepatitis C virus infection.
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.
Bain
Christine
C
FRE 2736 Ecole Normale Supérieure, Lyon, France.
Parroche
Peggy
P
Lavergne
Jean Pierre
JP
Duverger
Blandine
B
Vieux
Claude
C
Dubois
Valérie
V
Komurian-Pradel
Florence
F
Trépo
Christian
C
Gebuhrer
Lucette
L
Paranhos-Baccala
Glaucia
G
Penin
François
F
Inchauspé
Geneviève
G
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007156:Immunologic Memory; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008875:Middle Aged; D008969:Molecular Sequence Data; D012254:Ribavirin / Q000627:therapeutic use; D017385:Sequence Homology; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014766:Viremia
D000956:Antigens, Viral; D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D016898:Interferon-alpha; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus; D016753:Interleukin-10; D012254:Ribavirin; D007371:Interferon-gamma