Loss of the ITAM receptor CD200R1 attenuates HSV-1 infection and encephalitis. (68.15)

Abstract

Abstract We have discovered a novel role for the Immunoreceptor tyrosine-based activation motif (ITAM) containing receptor CD200R1 in virus infection. The host response to viral pathogens is driven by the activation of innate immune receptors that are triggered by pathogen-associated molecular pattern (PAMPs). These receptors include the transmembrane Toll-like receptors as well as the intracellular nucleic acid sensors RIG-I, Mda5, AIM2 and IFI16. ITAM receptors are known to both attenuate and activate signaling by innate receptors like TLRs but little is known about the potential impact of ITAMs on the outcome of viral infection. We generated CD200R1 knockout (KO) mice and infected with herpes simplex virus (HSV)-1. CD200R1 KO mice were protected from lethal HSV-1 encephalitis with >75% of the CD200R1 KOs surviving compared to 25% of the wild type (WT) mice, i.e., loss of CD200R1 conferred a survival advantage. This was not due to any obvious effects on the inflammatory response to infection. CD200R1 KO and WT mice had equivalent cytokine responses and leukocyte infiltration during the initial infection. Remarkably, HSV-1 virus replication was attenuated in CD200R1 KOs. Thus 50% of the CD200R1 KOs had cleared the virus from their brain by day 3-4 post-infection. In contrast, HSV-1 continued to replicate in the brains of 100% of the WT mice. Infection of cultured cells confirmed that CD200R1 expressing WT cells were more permissive for HSV-1 infection than CD200R1 KO cells.