Cell surface expression of major histocompatibility complex class I molecules is reduced in hepatitis C virus subgenomic replicon-expressing cells.
The hepatitis C virus (HCV) causes chronic hepatitis in most infected individuals by evading host immune defenses. In this investigation, we show that HCV-infected cells may go undetected in the immune system by suppressing major histocompatibility complex (MHC) class I antigen presentation to cytotoxic T lymphocytes. Cells expressing HCV subgenomic replicons have lower MHC class I cell surface expression. This is due to reduced levels of properly folded MHC class I molecules. HCV replicons induce endoplasmic reticulum (ER) stress (K. Tardif, K. Mori, and A. Siddiqui, J. Virol. 76:7453-7459, 2002), which results from a decline in protein glycosylation. Decreasing protein glycosylation can disrupt protein folding, preventing the assembly of MHC class I molecules. This results in the accumulation of unfolded MHC class I. Therefore, the persistence and pathogenesis of HCV may depend upon the ER stress-mediated interference of MHC class I assembly and cell surface expression.
Tardif
Keith D
KD
Department of Microbiology and Program in Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Siddiqui
Aleem
A
D004721:Endoplasmic Reticulum / Q000502:physiology; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D016679:Genome, Viral; D006031:Glycosylation; D016174:Hepacivirus / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017510:Protein Folding; D012093:Replicon / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D015395:Histocompatibility Antigens Class I