Hepatitis C virus inhibits CD4 T cell function via binding to Toll-like receptor 7

•Agonistic engagement of TLR7 reduces CD4 T cell functional activity.•Hepatitis C virus (HCV) inhibits CD4 T-cell IL2 and interferon γ production and expression of activation markers.•A TLR7 inhibitory oligonucleotide sequence reverts HCV-induced CD4 T cell anergy.•Viral RNA binding to TLR7 may be a general mechanism of RNA virus evasion from host's adaptive immunity.•The use of TLR7 agonists to treat chronic RNA virus infections could be counter-productive.

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.