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Journal of Virology, July 2007, p. 7801-7804, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00724-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Peptide-Mediated Interference with Influenza A Virus Polymerase{triangledown}

Alexander Ghanem,1 Daniel Mayer,1 Geoffrey Chase,1 Werner Tegge,2 Ronald Frank,2 Georg Kochs,1 Adolfo García-Sastre,3,4 and Martin Schwemmle1*

Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg,1 Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany,2 Department of Microbiology,3 Emerging Pathogens Institute, Box 1124, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, New York 100294

Received 4 April 2007/ Accepted 3 May 2007

The assembly of the polymerase complex of influenza A virus from the three viral polymerase subunits PB1, PB2, and PA is required for viral RNA synthesis. We show that peptides which specifically bind to the protein-protein interaction domains in the subunits responsible for complex formation interfere with polymerase complex assembly and inhibit viral replication. Specifically, we provide evidence that a 25-amino-acid peptide corresponding to the PA-binding domain of PB1 blocks the polymerase activity of influenza A virus and inhibits viral spread. Targeting polymerase subunit interactions therefore provides a novel strategy to develop antiviral compounds against influenza A virus or other viruses.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany. Phone: 49-761-203-6526. Fax: 49-761-203-6639. E-mail: martin.schwemmle{at}uniklinik-freiburg.de

{triangledown} Published ahead of print on 9 May 2007.

Journal of Virology, July 2007, p. 7801-7804, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.00724-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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