Roles of MAVs and MYD88 in Innate and Adaptive Immune Responses to Respiratory Syncytial Virus

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Roles of MAVs and MYD88 in Innate and Adaptive Immune Responses to Respiratory Syncytial Virus

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Title: Roles of MAVs and MYD88 in Innate and Adaptive Immune Responses to Respiratory Syncytial Virus
Author: Bhoj, Vijay Garud
Abstract: Detection of invading viruses by pathogen recognition receptors (PRRs) first illicits an innate immune response which includes the production of anti-viral interferons. TLRs 3, 4, and 7/8 and the RLR, RIG-I, are the primary PRRs involved in the recognition of RNA viruses and they signal through the adaptors TRIF (TLR3, 4), MyD88 (TLR4, 7/8, 9), and MAVS (RIG-I). The innate response serves to limit viral spread and to activate adaptive immune responses which eventually clear the infection. We dissected the contribution of TLR- and RLR- mediated recognition in the host response to Respiratory Syncytial Virus, a common human pathogen. Deletion of Mavs abolished the induction of type I interferon (IFN-I) and other pro-inflammatory cytokines by RSV. Genome-wide expression profiling in the lung showed that the vast majority of RSV-induced genes depended on MAVS. Although Myd88 deficiency did not affect most RSVinduced genes, mice lacking both adaptors harbored higher and more prolonged viral load and exhibited more severe pulmonary disease than those lacking either adaptor alone. Surprisingly, Myd88-/-Mavs-/- mice were able to activate a subset of pulmonary DCs which traffic to the draining lymph node in response to RSV. These mice subsequently mounted a normal cytotoxic T lymphocyte (CTL) response and demonstrated delayed but effective viral clearance. These results provide an example of a normal and effective adaptive immune response in the absence of innate immunity mediated by MAVS and MyD88.
URI: http://hdl.handle.net/2152.5/244
Date: 2010-05-14

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