Ganseerpel
Advisory Board, Senior Moderator
Cellular Microbiology
To cite this article: Igor Mazur, Walter J. Wurzer, Christina Ehrhardt, Stephan Pleschka, Pilaipan Puthavathana, Tobias Silberzahn, Thorsten Wolff, Oliver Planz, Stephan Ludwig
Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity
Cellular Microbiology (OnlineEarly Articles).
doi:10.1111/j.1462-5822.2007.00902.x
Accepted article online:
30 Jan 2007
Published article online:
23 Feb 2007
Original Article
Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity
* Igor Mazur,11Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
* Walter J. Wurzer,1+1Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.+Present address: Aventis Pharma, Saturn Tower, Leonard-Bernstein Strasse 10, A-1220 Vienna, Austria.
* Christina Ehrhardt,11Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
* Stephan Pleschka,22Institute of Medical Virology, Justus-Liebig-University, Frankfurter Strasse 107, D-35392 Giessen, Germany.
* Pilaipan Puthavathana,33Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
* Tobias Silberzahn,44Friedrich-Loeffler-Institute (FLI), Paul-Ehrlich-Strasse 28, D-72076 T?bingen, Germany.
* Thorsten Wolff,55Robert-Koch-Institute (RKI), Nordufer 20, D-13353 Berlin, Germany.
* Oliver Planz44Friedrich-Loeffler-Institute (FLI), Paul-Ehrlich-Strasse 28, D-72076 T?bingen, Germany.**E-mail ludwigs@uni-muenster.de; Tel. (+49) 251 83 57791; Fax (+49) 251 83 57793; E-mail oliver.planz@fli.bund.de; Tel. (+49) 7071 967 254; Fax (+49) 7071 967 105.These two authors have equally contributed to the study. and
* Stephan Ludwig11Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.**E-mail ludwigs@uni-muenster.de; Tel. (+49) 251 83 57791; Fax (+49) 251 83 57793; E-mail oliver.planz@fli.bund.de; Tel. (+49) 7071 967 254; Fax (+49) 7071 967 105.These two authors have equally contributed to the study.
*
1Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
2Institute of Medical Virology, Justus-Liebig-University, Frankfurter Strasse 107, D-35392 Giessen, Germany.
3Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
4Friedrich-Loeffler-Institute (FLI), Paul-Ehrlich-Strasse 28, D-72076 T?bingen, Germany.
5Robert-Koch-Institute (RKI), Nordufer 20, D-13353 Berlin, Germany.
*E-mail ludwigs@uni-muenster.de; Tel. (+49) 251 83 57791; Fax (+49) 251 83 57793; E-mail oliver.planz@fli.bund.de; Tel. (+49) 7071 967 254; Fax (+49) 7071 967 105.
Summary
Influenza is still one of the major plagues worldwide. The statistical likeliness of a new pandemic outbreak highlights the urgent need for new and amply available antiviral drugs. We and others have shown that influenza virus misuses the cellular IKK/NF-κB signalling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here we examined acetylsalicylic acid (ASA), also known as aspirin, a widely used drug with a well-known capacity to inhibit NF-κB. We show that the drug efficiently blocks influenza virus replication in vitro and in vivo in a mechanism involving impaired expression of proapoptotic factors, subsequent inhibition of caspase activation as well as block of caspase-mediated nuclear export of viral ribonucleoproteins. As ASA showed no toxic side-effects or the tendency to induce resistant virus variants, existing salicylate-based aerosolic drugs may be suitable as anti-influenza agents. This is the first demonstration that specific targeting of a cellular factor is a suitable approach for anti-influenza virus intervention.
To cite this article: Igor Mazur, Walter J. Wurzer, Christina Ehrhardt, Stephan Pleschka, Pilaipan Puthavathana, Tobias Silberzahn, Thorsten Wolff, Oliver Planz, Stephan Ludwig
Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity
Cellular Microbiology (OnlineEarly Articles).
doi:10.1111/j.1462-5822.2007.00902.x
Accepted article online:
30 Jan 2007
Published article online:
23 Feb 2007
Original Article
Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-κB-inhibiting activity
* Igor Mazur,11Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
* Walter J. Wurzer,1+1Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.+Present address: Aventis Pharma, Saturn Tower, Leonard-Bernstein Strasse 10, A-1220 Vienna, Austria.
* Christina Ehrhardt,11Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
* Stephan Pleschka,22Institute of Medical Virology, Justus-Liebig-University, Frankfurter Strasse 107, D-35392 Giessen, Germany.
* Pilaipan Puthavathana,33Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
* Tobias Silberzahn,44Friedrich-Loeffler-Institute (FLI), Paul-Ehrlich-Strasse 28, D-72076 T?bingen, Germany.
* Thorsten Wolff,55Robert-Koch-Institute (RKI), Nordufer 20, D-13353 Berlin, Germany.
* Oliver Planz44Friedrich-Loeffler-Institute (FLI), Paul-Ehrlich-Strasse 28, D-72076 T?bingen, Germany.**E-mail ludwigs@uni-muenster.de; Tel. (+49) 251 83 57791; Fax (+49) 251 83 57793; E-mail oliver.planz@fli.bund.de; Tel. (+49) 7071 967 254; Fax (+49) 7071 967 105.These two authors have equally contributed to the study. and
* Stephan Ludwig11Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.**E-mail ludwigs@uni-muenster.de; Tel. (+49) 251 83 57791; Fax (+49) 251 83 57793; E-mail oliver.planz@fli.bund.de; Tel. (+49) 7071 967 254; Fax (+49) 7071 967 105.These two authors have equally contributed to the study.
*
1Institute of Molecular Virology (IMV), ZMBE, Westfaelische-Wilhelms-University, Von-Esmarch-Street 56, D-48149 Muenster, Germany.
2Institute of Medical Virology, Justus-Liebig-University, Frankfurter Strasse 107, D-35392 Giessen, Germany.
3Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
4Friedrich-Loeffler-Institute (FLI), Paul-Ehrlich-Strasse 28, D-72076 T?bingen, Germany.
5Robert-Koch-Institute (RKI), Nordufer 20, D-13353 Berlin, Germany.
*E-mail ludwigs@uni-muenster.de; Tel. (+49) 251 83 57791; Fax (+49) 251 83 57793; E-mail oliver.planz@fli.bund.de; Tel. (+49) 7071 967 254; Fax (+49) 7071 967 105.
Summary
Influenza is still one of the major plagues worldwide. The statistical likeliness of a new pandemic outbreak highlights the urgent need for new and amply available antiviral drugs. We and others have shown that influenza virus misuses the cellular IKK/NF-κB signalling pathway for efficient replication suggesting that this module may be a suitable target for antiviral intervention. Here we examined acetylsalicylic acid (ASA), also known as aspirin, a widely used drug with a well-known capacity to inhibit NF-κB. We show that the drug efficiently blocks influenza virus replication in vitro and in vivo in a mechanism involving impaired expression of proapoptotic factors, subsequent inhibition of caspase activation as well as block of caspase-mediated nuclear export of viral ribonucleoproteins. As ASA showed no toxic side-effects or the tendency to induce resistant virus variants, existing salicylate-based aerosolic drugs may be suitable as anti-influenza agents. This is the first demonstration that specific targeting of a cellular factor is a suitable approach for anti-influenza virus intervention.
