title: Hepatitis C virus inhibits CD4 T cell function via binding to Toll-like receptor 7.
abstract: Toll-like receptor 7 (TLR7) is a ssRNA receptor that activates dendritic cells and macrophages upon ssRNA binding; however, little is known of its role in CD4+T cells. We show here that hepatitis C virus (HCV) induces a dose dependent inhibition of cytokine production and expression of activation markers in CD4 T cells, which were restored by a TLR7-specific antagonist. These findings indicate that HCV induces CD4 T cell impairment via TLR7 which may contribute to failure of virus eradication, casting doubts on the use of TLR7 agonists to boost innate immunity in chronic RNA virus infections.
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: d.mele@smatteo.pv.it.
authors.forename: Dalila
authors.initials: D
authors.lastname: Mele
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: s.mantovani@smatteo.pv.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mantovani
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: b.oliviero@smatteo.pv.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Oliviero
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: g.grossi@smatteo.pv.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Grossi
authors.affiliation: Internal Medicine and Hepatology Unit, Humanitas Research Hospital, Rozzano, Milan, Italy. Electronic address: serena.ludovisi@humanitas.it.
authors.forename: Serena
authors.initials: S
authors.lastname: Ludovisi
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. Electronic address: mario.mondelli@unipv.it.
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. Electronic address: s.varchetta@smatteo.pv.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Varchetta
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000096:biosynthesis; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D012367:RNA, Viral / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D051199:Toll-Like Receptor 7
keywords: CD4; HCV; IRS661; Imiquimod; TLR7