miR-144 attenuates the host response to influenza virus by targeting the TRAF6-IRF7 signaling axis
Carrie M. Rosenberger,Rebecca L. Podyminogin,Alan H. Diercks,Piper M. Treuting,Jacques J. Peschon,David Rodriguez,Madhumati Gundapuneni,Mitchell J. Weiss,Alan Aderem +8 more
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TLDR
It is suggested that miR-144 reduces the antiviral response by attenuating the TRAF6-IRF7 pathway to alter the cellular antiviral transcriptional landscape.Abstract:
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.read more
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References
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IRF-7 is the master regulator of type-I interferon-dependent immune responses
Kenya Honda,Hideyuki Yanai,Hideo Negishi,Masataka Asagiri,Mitsuharu Sato,Tatsuaki Mizutani,Naoya Shimada,Yusuke Ohba,Yusuke Ohba,Akinori Takaoka,Nobuaki Yoshida,Tadatsugu Taniguchi +11 more
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