Non-neutralizing epitopes induce robust hepatitis C virus (HCV)-specific antibody-dependent CD56+ natural killer cell responses in chronic HCV-infected patients. (7th April 2017)

• Record Type: Journal Article
• Authors: Long, L; Jia, M; Fan, X; Liang, H; Wang, J; Zhu, L; Xie, Z; Shen, T
• Is Part Of: Clinical and experimental immunology. Volume 189:Number 1(2017:Jul.)
• Page Start: 92
• Page End: 102
• Publication Date: 2017-04-07
• Subjects: antibody-dependent cellular cytotoxicity -- epitope -- hepatitis C virus -- natural killer cell -- non-neutralizing antibody; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12962
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC) is of considerable interest in viral infection. However, little is known about NK-ADCC responses in chronic hepatitis C virus (HCV) infection. In this study, impaired non-specific antibody-dependent CD56 + NK cell responses were observed in chronic HCV infection, as shown by decreased degranulation (extracellular CD107a expression) and interferon (IFN)-γ production in response to antibody-bound P815 cells. A peptide pool composed of epitopes recognized by anti-HCV-E1/E2 antibodies could induce pronounced HCV-specific antibody-dependent NK cell responses in sera from approximately half the chronic HCV carriers. Additionally, HCV-specific epitopes with the capacity to induce robust NK-ADCC activity were identified. Five linear NK-ADCC epitopes (aa211-aa217, aa384-aa391, aa464-aa475, aa544-aa551 and aa648-aa659 of the HCV envelope) were identified and do not overlap with putative linear neutralizing epitopes. This study revealed the dysfunctional characteristics of antibody-dependent CD56 + NK cell responses in chronic HCV carriers. The key non-neutralizing NK-ADCC epitopes identified in this study may act as new targets for immunological intervention. Graphical Abstract: