miR-144 attenuates the host response to influenza virus by targeting the TRAF6-IRF7 signaling axis

Carrie M Rosenberger1, Rebecca L Podyminogin1, Alan H Diercks1

  • 1Center for Infectious Disease Research, Seattle, WA United States of America.

Plos Pathogens
|April 6, 2017
PubMed

Insights

MicroRNAs (miRNAs) regulate cellular responses. This study identifies miR-144 as a key negative regulator of the host antiviral response, impacting viral replication and disease severity.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Antiviral responses are crucial for host defense but require tight regulation to prevent excessive inflammation.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally.
  • Mechanisms controlling the magnitude of antiviral responses within infected cells remain incompletely understood.

Purpose of the Study:

  • To identify novel regulators of the host antiviral response.
  • To investigate the role of microRNAs in modulating antiviral immunity.
  • To elucidate the specific molecular pathways targeted by identified regulators.

Main Methods:

  • Ectopic expression of miR-144 in primary mouse lung epithelial cells.
  • Assessment of viral replication for influenza virus, EMCV, and VSV.
  • Identification of the transcriptional network regulated by miR-144.
  • Analysis of TRAF6 and IRF7 pathway involvement.
  • In vivo studies using miR-144 knockout mice to evaluate influenza virus infection.

Main Results:

  • Ectopic miR-144 expression enhanced replication of multiple RNA viruses (influenza, EMCV, VSV).
  • miR-144 was found to post-transcriptionally suppress levels of TRAF6 (TNF receptor-associated factor 6).
  • In vivo ablation of miR-144 significantly reduced influenza virus replication and disease severity in mouse lungs.
  • miR-144 attenuates the TRAF6-IRF7 pathway, altering the cellular antiviral transcriptional landscape.

Conclusions:

  • miR-144 acts as a negative regulator of the host antiviral response.
  • Suppression of TRAF6 by miR-144 dampens the antiviral signaling cascade.
  • Targeting miR-144 may represent a therapeutic strategy to enhance antiviral immunity and reduce disease severity.

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