Focal Adhesion Kinase Is a Component of Antiviral RIG-I-like Receptor Signaling

Rebecca A. Bozym, et al. 2012. Cell Host & Microbe. 11, 153-66.

Speaker: Yu-Zhen Lu (呂瑜珍)                             Time: 15:00~16:00, Nov. 7, 2012

Commentator: Dr. Pin Ling (凌斌 博士)             Place: Room 601

Abstract:

Retinoic acid inducible gene-I (RIG-I) and melanoma differentiation associated gene 5 (MDA5), as members of RIG-I-like receptor (RLR) family, recognize viral dsRNA and activate mitochondrial antiviral signaling (MAVS) that triggers NF-ҡB activatopn and type I IFN production. Besides, actin cytoskeleton also provides a physical barrier to protect host cell from pathogen infection. Viruses need to disrupt the structure of cytoskeleton for entry and egress. Previous studies indicated that perturbations of the cytoskeleton will be detected by host cells and induce RLR signaling pathway for eliminating viruses. Focal adhesion kinase (FAK) is a protein tyrosine kinase which transmits signaling between the extracellular matrix and the cytoplasma. FAK-mediated signaling regulates many downstream responses, including cytoskeletal reorganization. In this study, the authors wanted to investigate if FAK participates in the RLR-mediated signaling. They showed that mouse embryonic fibroblasts (MEF) deficient in FAK are more sensitive to RNA virus infection and unable to induce NF-ҡB activation and IFNβ production. Following viral infection, FAK is recruited to mitochondria membrane and interacted with MAVS and other components which are involving in the RLR signaling. In FAK^+/+ MEF, MAVS consisted of large cytoplasmic aggregates after viral infection. However, in FAK^-/-  MEF, MAVS formed large clusters within the cytoplasma, and that remained unchanged after viral infection. These data showed that FAK participates in some aspect of MAVS localization and influences the immune response. The authors also found the coxsackievirus B (CVB) encodes 3C^pro cysteine protease, which directly cleaves FAK as a way to evade host innate immunity. Taken together, this article identified a new role for FAK in RLR-mediated antiviral signaling.

References:

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