title: Induction of interferon-γ contributes to Toll-like receptor 3-mediated herpes simplex virus type 1 inhibition in astrocytes.
abstract: Toll-like receptor 3 (TLR3) recognizes double-stranded RNA and induces type I interferon (IFN)-mediated antiviral immunity against a number of viral infections. Type III IFN (IFN-λ) is a newly identified antiviral cytokine that has biological functions similar to those of type I IFNs. We thus investigated the role of IFN-λ in TLR3 activation-mediated inhibition of herpes simplex virus type 1 (HSV-1) in human primary astrocytes. Human astrocytes express endogenous IFN-λ1 and IFN-λ receptor complex, interleukin-28 receptor α subunit (IL-28Rα), and IL-10Rβ. The activation of TLR3 by poly-I:C treatment significantly induced the expression of IFN-λ1 and IFN-λ2/3 in astrocytes. The induction of IFN-λ contributed to TLR3 activation-mediated HSV-1 inhibition in astrocytes. Investigation of the mechanisms showed that treatment of astrocytes with specific antibody against IFN-λ receptor attenuated the anti-HSV-1 activity of poly-I:C, indicating that endogenous IFN-λ contributes to the anti-HSV-1 effect of TLR3 activation. The anti-HSV-1 effect of endogenous IFN-λ was also confirmed by the finding that recombinant IFN-λ treatment inhibited HSV-1 infection of astrocytes. These results provide direct and compelling evidence that endogenous IFN-λ participates in TLR3-mediated antiviral activity, which may have important implications in host cell innate immunity against HSV-1 infection in the CNS.
authors: Animal Biosafety Level 3 Laboratory, Wuhan University, Wuhan, People's Republic of China.
authors: Jieliang
authors: J
authors: Li
authors: Li
authors: L
authors: Ye
authors: Xu
authors: X
authors: Wang
authors: Shuxian
authors: S
authors: Hu
authors: Wenzhe
authors: W
authors: Ho
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology* / Q000821:virology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000502:physiology; D011817:Rabbits; D051196:Toll-Like Receptor 3 / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007371:Interferon-gamma