The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment
Name
Hanke-2016-The Antiviral Mechanism of an Influ.pdf
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2.22 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Hanke, Leo
Brewer, R. Camille
van Diest, Eline
Schmidt, Florian I.
Schwartz, Thomas
Knockenhauer, Kevin Edward
Ploegh, Hidde
Date Issued
December 2016
Journal
mBio
Publisher
American Society for Microbiology
Citation
Hanke, Leo et al. “The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment.” mBio 7.6 (2016): e01569-16.
Version
Final published version
Abstract
Alpaca-derived single-domain antibody fragments (VHHs) that target the influenza A virus nucleoprotein (NP) can protect cells from infection when expressed in the cytosol. We found that one such VHH, αNP-VHH1, exhibits antiviral activity similar to that of Mx proteins by blocking nuclear import of incoming viral ribonucleoproteins (vRNPs) and viral transcription and replication in the nucleus. We determined a 3.2-Å crystal structure of αNP-VHH1 in complex with influenza A virus NP. The VHH binds to a nonconserved region on the body domain of NP, which has been associated with binding to host factors and serves as a determinant of host range. Several of the NP/VHH interface residues determine sensitivity of NP to antiviral Mx GTPases. The structure of the NP/αNP-VHH1 complex affords a plausible explanation for the inhibitory properties of the VHH and suggests a rationale for the antiviral properties of Mx proteins. Such knowledge can be leveraged for much-needed novel antiviral strategies.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1128/mBio.01569-16
