AbstractsMedical & Health Science

Influenza Resistance to Antiviral Drugs: Virus characterization, mechanism and clinical impact

by E. van der Vries (Erhard)




Institution: Erasmus University
Department:
Year: 2014
Keywords: Influenza; Antiviral resistance; Oseltamivir; Tamiflu; zanamivir; Relenza; H1N1; H3N2; pandemic; neuraminidase; hemagglutitinin; H275Y; RT-PCR
Record ID: 1241479
Full text PDF: http://hdl.handle.net/1765/50389


Abstract

abstract__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.markdown