Using MicroRNA knowledge for safer influenza virus research and potentially better vaccines

MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies

Article Summary: Recent gain-of-function studies in influenza A virus H5N1 strains revealed that as few as three-amino-acid changes in the hemagglutinin protein confer the capacity for viral transmission between ferrets1, 2. As transmission between ferrets is considered a surrogate indicator of transmissibility between humans, these studies raised concerns about the risks of gain-of-function influenza A virus research. Here we present an approach to strengthen the biosafety of gain-of-function influenza experiments. We exploit species-specific endogenous small RNAs to restrict influenza A virus tropism. In particular, we found that the microRNA miR-192 was expressed in primary human respiratory tract epithelial cells as well as in mouse lungs but absent from the ferret respiratory tract. Incorporation of miR-192 target sites into influenza A virus did not prevent influenza replication and transmissibility in ferrets, but did attenuate influenza pathogenicity in mice. This molecular biocontainment approach should be applicable beyond influenza A virus to minimize the risk of experiments involving other pathogenic viruses.

@ MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies : Nature Biotechnology : Nature Publishing Group:

Ryan A Langlois, Randy A Albrecht, Brian Kimble, Troy Sutton, Jillian S Shapiro, Courtney Finch, Matthew Angel, Mark A Chua, Ana Silvia Gonzalez-Reiche, Kemin Xu, Daniel Perez,Adolfo García-Sastre
& Benjamin R tenOever Affiliations
Contributions
Corresponding authorsNature Biotechnology (2013) doi:10.1038/nbt.2666Received 23 April 2013 Accepted 19 July 2013 Published online 11 August 2013

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