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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Membrane perturbation elicits an IRF3-dependent, interferon-independent antiviral response
Ryan S Noyce1, Kathryne Taylor, Marta Ciechonska
1Department of Biochemistry and Biomedical Sciences, Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
Abstract:
We previously found that enveloped virus binding and penetration are necessary to initiate an interferon-independent, IRF3-mediated antiviral response. To investigate whether membrane perturbations that accompany membrane fusion-dependent enveloped-virus entry are necessary and sufficient for antiviral-state induction, we utilized a reovirus fusion-associated small transmembrane (FAST) protein. Membrane disturbances during FAST protein-mediated fusion, in the absence of additional innate immune response triggers, are sufficient to elicit interferon-stimulated gene induction and establishment of an antiviral state. Using sensors of membrane disruption to activate an IRF3-dependent, interferon-independent antiviral state may provide cells with a rapid, broad-spectrum innate immune response to enveloped-virus infections.
Insights
Membrane disturbances from enveloped viruses can trigger an antiviral state. This interferon-independent response, mediated by IRF3, offers rapid protection against viral infections.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Enveloped virus entry triggers an interferon-independent, IRF3-mediated antiviral response.
- The role of membrane fusion and associated perturbations in initiating this response was unclear.
Purpose of the Study:
- To determine if membrane perturbations during enveloped virus entry are necessary and sufficient for inducing an antiviral state.
- To investigate the potential of using membrane disruption sensors for rapid antiviral responses.
Main Methods:
- Utilized a reovirus fusion-associated small transmembrane (FAST) protein to induce membrane fusion and perturbations.
- Assessed the induction of interferon-stimulated genes and the establishment of an antiviral state in the absence of other innate immune triggers.
Main Results:
- Membrane disturbances induced by FAST protein-mediated fusion were sufficient to elicit interferon-stimulated gene induction.
- An antiviral state was established solely through membrane fusion events, independent of other innate immune triggers.
Conclusions:
- Membrane perturbations, not just viral binding and penetration, are sufficient to initiate an IRF3-dependent, interferon-independent antiviral state.
- Harnessing sensors of membrane disruption could lead to rapid, broad-spectrum innate immune responses against enveloped viruses.
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