Inhibition of major histocompatibility complex Class I antigen presentation by hepatitis C virus core protein in myeloid dendritic cells

Hepatitis C virus core (HCVcore) protein was expressed in myeloid dendritic cells (DC) from C57/B6 mice (H-2Kb) by electroporation of HCVcore mRNA to investigate its effect on the ability of DC to prime CD8+ T cells displaying a T cell receptor specific for OVA257–264 peptide (SIINFEKL)/H-2Kb complex. Expression of full length HCVcore191, which is directed to the endoplasmic reticulum (ER) membrane by a C-terminal signal sequence, but not a truncated variant HCVcore152, which has a wider subcellular localization including the nucleus, significantly reduced surface levels of the H-2Kb/SIINFEKL complex and impaired the ability of DC to prime naïve CD8+ T cells when they had to process endogenous antigen but not when MHC class I molecules were loaded directly with SIINFEKL peptide. Exploitation of the MHC class I antigen-processing pathway by HCVcore191 impairs the ability of DC to stimulate CD8+ T cells and may contribute to the persistence of HCV infection.