Understanding Influenza Virus Resistance to Antiviral Agents; Early Warning Signs for Wider Community Circulation

(See the article by Hurt et al, on pages 148-57.) Influenza viruses circulating among humans vary genetically from season to season and even within a season in different regions of the world. Thus, global surveillance for influenza viruses is critical to monitor for antigenic changes in circulating influenza viruses and to inform annual vaccine strain selection. In addition, surveillance is critical to monitor for virus susceptibility to antiviral drugs. Resistance to the adamantane class of drugs (amantadine and rimantadine), caused by substitutions at key amino acid residues in the M2 protein, has been widespread among influenza A viruses [1]. Adamantanes are not effective against currently circulating A(H3N2) viruses and 2009 pandemic influenza A(H1N1) (H1N1pdm09) viruses because of the S31N change in the M2 protein [2, 3]. Resistance to both approved neuraminidase (NA) inhibitors, oseltamivir and zanamivir, has been occasionally reported for all influenza virus A subtypes and influenza B viruses affecting humans [4]; however, widespread global circulation of influenza viruses resistant to an NA inhibitor (NAI) has occurred only once since the initiation of surveillance for NAI resistance in 1999 [5].