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

PLoS Pathogens

Jacques J. Peschon¹  David Rodriguez¹  Rebecca L. Podyminogin¹  Carrie M. Rosenberger¹  Alan H. Diercks¹  Alan Aderem¹  Piper M. Treuting²  Mitchell J. Weiss³  Madhumati Gundapuneni⁴ 

[1] Center for Infectious Disease Research, Seattle, WA United States of America;Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, United States of America;Hematology, St. Jude Children's Research Hospital, Memphis, TN United States of America;Institute for Systems Biology, Seattle, WA, United States of America

关键词: Influenza viruses;    MicroRNAs;    Epithelial cells;    Gene expression;    Viral replication;    Infectious disease control;    Viral load;    Viral gene expression;   

DOI  :  10.1371/journal.ppat.1006305

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Antiviral responses must rapidly defend against infection while minimizing inflammatory damage, but the mechanisms that regulate the magnitude of response within an infected cell are not well understood. miRNAs are small non-coding RNAs that suppress protein levels by binding target sequences on their cognate mRNA. Here, we identify miR-144 as a negative regulator of the host antiviral response. Ectopic expression of miR-144 resulted in increased replication of three RNA viruses in primary mouse lung epithelial cells: influenza virus, EMCV, and VSV. We identified the transcriptional network regulated by miR-144 and demonstrate that miR-144 post-transcriptionally suppresses TRAF6 levels. In vivo ablation of miR-144 reduced influenza virus replication in the lung and disease severity. These data suggest that miR-144 reduces the antiviral response by attenuating the TRAF6-IRF7 pathway to alter the cellular antiviral transcriptional landscape.

【 授权许可】

CC BY