title: Influenza virus resistance to antiviral therapy.
abstract: Antiviral drugs for influenza therapy and prophylaxis are either of the adamantane or neuraminidase inhibitor (NAI) class. However, the NAIs are mainly prescribed nowadays, because of widespread adamantane resistance among influenza A viruses and ineffectiveness of adamantanes against influenza B. Emergence and spread of NAI resistance would further limit our therapeutic options. Taking into account the previous spread of oseltamivir-resistant viruses during the 2007/2008 season preceding the last pandemic, emergence of yet another naturally NAI-resistant influenza virus may not be an unlikely event. This previous incident also underlines the importance of resistance surveillance and asks for a better understanding of the mechanisms underlying primary resistance development. We provide an overview of the major influenza antiviral resistance mechanisms and future therapies for influenza. Here, we call for a better understanding of the effect of virus mutations upon antiviral treatment and for a tailored antiviral approach to severe influenza virus infections.
authors.affiliation: Viroscience Lab, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Erhard
authors.initials: E
authors.lastname: van der Vries
authors.forename: Martin
authors.initials: M
authors.lastname: Schutten
authors.forename: Pieter
authors.initials: P
authors.lastname: Fraaij
authors.forename: Charles
authors.initials: C
authors.lastname: Boucher
authors.forename: Albert
authors.initials: A
authors.lastname: Osterhaus
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000235:genetics; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology
chemical_list: D000998:Antiviral Agents; D015507:Drugs, Investigational; D009439:Neuraminidase
keywords: H1N1; H274Y; H3N2; I222R; Influenza; Neuraminidase; Oseltamivir; R292K; Resistance; Zanamivir