The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit

Alexandre Dias, Denis Bouvier, Thibaut Crépin, Andrew A. McCarthy, Darren J. Hart, Florence Baudin, Stephen Cusack () and Rob W. H. Ruigrok
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Alexandre Dias: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Denis Bouvier: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Thibaut Crépin: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Andrew A. McCarthy: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Darren J. Hart: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Florence Baudin: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Stephen Cusack: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France
Rob W. H. Ruigrok: Unit of Virus Host-Cell Interactions, UJF-EMBL-CNRS, UMR 5233, 6 rue Jules Horowitz, BP181, 38042 Grenoble Cedex 9, France

Nature, 2009, vol. 458, issue 7240, 914-918

Abstract: Avian flu virus polymerase The influenza virus RNA-dependent RNA polymerase, which contains three subunits (PA, PB1 and PB2), directs the replication and transcription of viral RNA inside the nuclei of infected cells. Two groups now report the crystal structure of the N terminus of the PA subunit of avian influenza virus. Structural comparison and mutational analysis show that the PA subunit contains an endonucleolytic cleavage site, an activity previously suspected to reside on the PB1 subunit. The PA endonuclease active site is highly conserved across influenza strains, making it a promising potential target for new anti-influenza drugs.

Date: 2009
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DOI: 10.1038/nature07745

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