Title
T Cell Dysfunction by Hepatitis C Virus Core Protein Involves PD-1/Pdl-1 Signaling
Document Type
Article
Publication Date
7-23-2007
Description
Reports have shown that a negative T cell costimulatory pathway mediated by PD-1 (programmed death-1) and PDL-1 (programmed death ligand-1) is associated with T cell exhaustion and persistent viral infection. Persistent hepatitis C virus (HCV) infection in humans is also characterized by impaired T lymphocyte function, but the role of the PD-1 and PDL-1 pathway in HCV infection is unknown. Here we report that T cells isolated from chronically HCV-infected patients express significantly higher levels of PD-1 when compared with healthy donors. In addition, PD-1 and PDL-1 expression is upregulated on healthy donor T cells exposed to HCV core, a nucleocapsid protein that is immunosuppressive; upregulation of PD-1 is mediated through interaction of HCV core with the complement receptor, gC1qR. Importantly, T cell functions that are dysregulated by HCV core, including T cell activation, proliferation, and apoptosis, can be restored by blocking PD-1 and PDL-1 engagement. Our results indicate that HCV core can upregulate a key negative T cell signaling pathway associated with viral persistence and highly expressed on the T cells of persistently infected individuals. This upregulation of the PD-1 and PDL-1 pathway in humans represents a novel and perhaps common mechanism by which a virus usurps host machinery to facilitate persistence.
Citation Information
Yao, Zhi Q.; King, Ellis; Prayther, Deborah; Yin, Deling; and Moorman, Jonathan. 2007. T Cell Dysfunction by Hepatitis C Virus Core Protein Involves PD-1/Pdl-1 Signaling. Viral Immunology. Vol.20(2). 276-287. https://doi.org/10.1089/vim.2006.0096 PMID: 17603844 ISSN: 0882-8245