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.

Journal of Virology
|August 5, 2011
PubMed

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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