title: Interferon-alpha treatment induces delayed CD4 proliferative responses to the hepatitis C virus nonstructural protein 3 regardless of the outcome of therapy.
abstract: The proliferative responses to a hepatitis C virus (HCV) recombinant nonstructural protein 3 (rNS3) were analyzed in 9 patients with chronic HCV infection before, during, and after 24 weeks of treatment with interferon-alpha (IFN-alpha) alone or in combination with ribavirin. Regardless of the therapy and the subsequent outcome, all patients showed an increased rNS3-specific proliferative response in peripheral blood mononuclear cells in vitro within 48 weeks from the start of therapy (P < .01). The proliferating cell phenotype was CD4 and was dependent on HLA-DP/DQ/DR class II antigen presentation. rNS3 induced in vitro detectable interleukin (IL)-2, IL-10, and IFN-gamma production in some patients before or after therapy (or both). No significant differences existed between responders and relapsed responders plus nonresponders with respect to the NS3-specific CD4 T helper (Th) cell responses. Thus, IFN-alpha therapy induces HCV NS3-specific CD4 Th cell proliferation regardless of the outcome of therapy.
authors.affiliation: Division of Clinical Virology, Huddinge University Hospital, Sweden.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Zhang
authors.forename: D R
authors.initials: DR
authors.lastname: Milich
authors.forename: D L
authors.initials: DL
authors.lastname: Peterson
authors.forename: A
authors.initials: A
authors.lastname: Birkett
authors.forename: R
authors.initials: R
authors.lastname: Schvarcz
authors.forename: O
authors.initials: O
authors.lastname: Weiland
authors.forename: M
authors.initials: M
authors.lastname: Sällberg
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins / Q000494:pharmacology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D018937:Hepatitis C Antibodies; D016898:Interferon-alpha; D007371:Interferon-gamma; D016753:Interleukin-10; D007376:Interleukin-2; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases