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

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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 ferrets. 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.

Original languageEnglish (US)
Pages (from-to)844-847
Number of pages4
JournalNature Biotechnology
Volume31
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Fingerprint

Influenza A virus
MicroRNAs
Ferrets
Viruses
Human Influenza
Respiratory System
Tropism
Hemagglutinins
Virulence
RNA
Epithelial Cells
Amino acids
Amino Acids
Experiments
Lung
Proteins
Research

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Biotechnology
  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering

Cite this

Langlois, R. A., Albrecht, R. A., Kimble, B., Sutton, T., Shapiro, J. S., Finch, C., ... Tenoever, B. R. (2013). MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nature Biotechnology, 31(9), 844-847. https://doi.org/10.1038/nbt.2666

MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. / Langlois, Ryan A.; Albrecht, Randy A.; Kimble, Brian; Sutton, Troy; Shapiro, Jillian S.; Finch, Courtney; Angel, Matthew; Chua, Mark A.; Gonzalez-Reiche, Ana Silvia; Xu, Kemin; Perez, Daniel; García-Sastre, Adolfo; Tenoever, Benjamin R.

In: Nature Biotechnology, Vol. 31, No. 9, 09.2013, p. 844-847.

Research output: Contribution to journalArticle

Langlois, RA, Albrecht, RA, Kimble, B, Sutton, T, Shapiro, JS, Finch, C, Angel, M, Chua, MA, Gonzalez-Reiche, AS, Xu, K, Perez, D, García-Sastre, A & Tenoever, BR 2013, 'MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies', Nature Biotechnology, vol. 31, no. 9, pp. 844-847. https://doi.org/10.1038/nbt.2666
Langlois RA, Albrecht RA, Kimble B, Sutton T, Shapiro JS, Finch C et al. MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nature Biotechnology. 2013 Sep;31(9):844-847. https://doi.org/10.1038/nbt.2666
Langlois, Ryan A. ; Albrecht, Randy A. ; Kimble, Brian ; Sutton, Troy ; Shapiro, Jillian S. ; Finch, Courtney ; Angel, Matthew ; Chua, Mark A. ; Gonzalez-Reiche, Ana Silvia ; Xu, Kemin ; Perez, Daniel ; García-Sastre, Adolfo ; Tenoever, Benjamin R. / MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. In: Nature Biotechnology. 2013 ; Vol. 31, No. 9. pp. 844-847.
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