Abstract

Each year, approximately 5-10% of the world population is infected with the influenza viruses resulting in significant morbidity and an estimated 250.000 to 500.000 deaths every year. Among individuals at increased risk of developing severe influenza disease are those with a compromised immune system. For them being able to effectively suppress viral replication antiviral therapy can be crucial. However, in immunocompromised patients the currently available antiviral drugs show limited effectiveness. The emergence and spread of antiviral resistant viruses limit current therapeutic intervention even more. The aim of this thesis is to improve our understanding of influenza antiviral resistance. We developed new molecular tools to aid in influenza patient management, characterised a novel I222R antiviral resistance mutation and developed an immunocompromised ferret model. Finally, a key role for the influenza hemagglutinin in neuraminidase inhibitor resistance is proposed in the general discussion of this thesis. The contribution of the hemagglutinin in neuraminidase inhibitor resistance may explain the emergence of the H274Y oseltamivir-resistant influenza A/H1N1 virus in the winter season of 2007/2008.

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A.D.M.E. Osterhaus (Albert) , C.A.B. Boucher (Charles)
Erasmus University Rotterdam , The research described in this thesis was conducted at the Viroscience lab of the Erasmus MC, the Netherlands and at the National Institute of Medical Research, Mill Hill, UK. It was carried out within the framework of the Influenza Resistance Information (IRIS) Study (NCT00884117) supported by Hoffman-La Roche Ltd., and the Erasmus Postgraduate School of Molecular Medicine. Financial support for printing of this thesis from Viroclinics Biosciences B.V., Virology education, Voorthuyzen Coaching & Advies and Qia gen, is gratefully acknowledged.
hdl.handle.net/1765/50389
Erasmus MC: University Medical Center Rotterdam

van der Vries, E. (2014, January 24). Influenza Resistance to Antiviral Drugs: Virus characterization, mechanism and clinical impact. The research described in this thesis was conducted at the Viroscience lab of the Erasmus MC, the Netherlands and at the National Institute of Medical Research, Mill Hill, UK. It was carried out within the framework of the Influenza Resistance Information (IRIS) Study (NCT00884117) supported by Hoffman-La Roche Ltd., and the Erasmus Postgraduate School of Molecular Medicine. Financial support for printing of this thesis from Viroclinics Biosciences B.V., Virology education, Voorthuyzen Coaching & Advies and Qia gen, is gratefully acknowledged. Retrieved from http://hdl.handle.net/1765/50389