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Updated: May 24, 2026

Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling
Rebecca A Bozym1, Elizabeth Delorme-Axford, Katharine Harris
1Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Abstract:
Viruses modulate the actin cytoskeleton at almost every step of their cellular journey from entry to egress. Cellular sensing of these cytoskeletal changes may function in the recognition of viral infection. Here we show that focal adhesion kinase (FAK), a focal adhesion localized tyrosine kinase that transmits signals between the extracellular matrix and the cytoplasm, serves as a RIG-I-like receptor antiviral signaling component by directing mitochondrial antiviral signaling adaptor (MAVS) activation. Cells deficient in FAK are highly susceptible to RNA virus infection and attenuated in antiviral signaling. We show that FAK interacts with MAVS at the mitochondrial membrane in a virus infection-dependent manner and potentiates MAVS-mediated signaling via a kinase-independent mechanism. A cysteine protease encoded by enteroviruses cleaves FAK to suppress its role in innate immune signaling. These findings suggest that FAK serves as a link between cytoskeletal perturbations that occur during virus infection and activation of innate immune signaling.
Insights
Focal adhesion kinase (FAK) links viral actin cytoskeleton changes to innate immune signaling by activating MAVS. Enteroviruses cleave FAK, suppressing this antiviral response.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Viruses manipulate the host actin cytoskeleton during infection.
- Cellular detection of cytoskeletal alterations may be crucial for recognizing viral infections.
- Focal adhesion kinase (FAK) is a key signaling molecule in cellular processes.
Purpose of the Study:
- To investigate the role of FAK in antiviral innate immune signaling.
- To determine how FAK interacts with antiviral signaling pathways.
- To understand how viruses might evade FAK-mediated antiviral responses.
Main Methods:
- Utilized FAK-deficient cells to assess susceptibility to viral infection.
- Investigated FAK interaction with mitochondrial antiviral signaling adaptor (MAVS) during infection.
- Examined the effect of viral protease activity on FAK function.
Main Results:
- FAK-deficient cells exhibit increased susceptibility to RNA virus infection and impaired antiviral signaling.
- FAK interacts with MAVS at the mitochondrial membrane in a virus-dependent manner.
- FAK potentiates MAVS signaling independently of its kinase activity.
- Enterovirus cysteine proteases cleave FAK, inhibiting its innate immune signaling role.
Conclusions:
- FAK acts as a crucial component of the RIG-I-like receptor antiviral signaling pathway.
- FAK bridges the sensing of virus-induced cytoskeletal changes to MAVS activation.
- Viral manipulation of FAK is a mechanism to suppress innate antiviral immunity.
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