Induction of Interferon-λ Contributes to Toll-Like Receptor 3-Mediated Herpes Simplex Virus Type 1 Inhibition in Astrocytes

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-lambda) is a newly identified antiviral cytokine that has biological functions similar to those of type I IFNs. We thus investigated the role of IFN-lambda in TLR3 activation-mediated inhibition of herpes simplex virus type 1 (HSV-1) in human primary astrocytes. Human astrocytes express endogenous IFN-lambda 1 and IFN-lambda receptor complex, interleukin-28 receptor alpha subunit (IL-28R alpha), and IL-10R beta. The activation of TLR3 by poly-I:C treatment significantly induced the expression of IFN-lambda 1 and IFN-lambda 2/3 in astrocytes. The induction of IFN-lambda contributed to TLR3 activation-mediated HSV-1 inhibition in astrocytes. Investigation of the mechanisms showed that treatment of astrocytes with specific antibody against IFN-lambda receptor attenuated the anti-HSV-1 activity of poly-I: C, indicating that endogenous IFN-lambda contributes to the anti-HSV-1 effect of TLR3 activation. The anti-HSV-1 effect of endogenous IFN-lambda was also confirmed by the finding that recombinant IFN-lambda treatment inhibited HSV-1 infection of astrocytes. These results provide direct and compelling evidence that endogenous IFN-lambda participates in TLR3-mediated antiviral activity, which may have important implications in host cell innate immunity against HSV-1 infection in the CNS. (C) 2011 Wiley Periodicals, Inc.