title: A novel T cell evasion mechanism in persistent RNA virus infection.
abstract: Hepatitis C virus (HCV) and GB virus type C (GBV-C) are associated with impaired T cell function despite the fact that HCV replicates in hepatocytes and GBV-C in a small proportion of lymphocytes. Recently, we showed that HCV and GBV-C E2-envelope proteins reduce T cell activation via the T cell receptor (TCR) by competing for phosphorylation with a critical kinase in the TCR signaling cascade (Lck). E2 interfered with TCR signaling in E2 expressing cells and in bystander cells. The bystander effect was mediated by virus particles and extracellular microvesicular particles (exosomes). Multiple kinase substrate sites are predicted to reside on viral structural proteins and based on bioinformatic predictions, many RNA virus pathogens may interfere with TCR signaling via a similar mechanism. Identification of T cell inhibitory effects of virus structural proteins may provide novel approaches to enhance the immunogenicity and memory of viral vaccines.
authors.affiliation: Iowa City, IA.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
authors.affiliation: Iowa City, IA.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Iowa City, IA.
authors.forename: James H
authors.initials: JH
authors.lastname: McLinden
authors.affiliation: Iowa City, IA.
authors.forename: Nirjal
authors.initials: N
authors.lastname: Bhattarai
authors.affiliation: Iowa City, IA.
authors.forename: Ernest T
authors.initials: ET
authors.lastname: Chivero
authors.affiliation: Iowa City, IA.
authors.forename: Donna
authors.initials: D
authors.lastname: Klinzman
authors.affiliation: Iowa City, IA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kaufman
authors.affiliation: Iowa City, IA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
mesh_terms: D000818:Animals; D029407:GB virus C / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D016174:Hepacivirus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D006505:Hepatitis / Q000453:epidemiology / Q000266:history / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D049673:History, 20th Century; D049674:History, 21st Century; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D014759:Viral Envelope Proteins; C107619:glycoprotein E2, GB virus C; C091015:glycoprotein E2, Hepatitis C virus