H1N1 antiviral resistance

Abstract

From April 2009 to the present, the influenza A(H1N1)pdm09 virus has been evolving continuously, acquiring new amino acid changes that may alter its antigenic characteristics, virulence, and its antiviral drug susceptibility. Phylogenetic analysis of the hemagglutinin (HA) gene of A(H1N1)pdm09 viruses showed that it clustered into 8 genetic groups relative to A/California/7/2009, in addition to others reported by regional influenza surveillance networks. However, none were considered antigenically distinct from the vaccine virus A/California/7/2009, which was recommended for use during the 2012–2013 influenza season in the Northern Hemisphere. Amino acid substitution D222G in the HA1 subunit of HA was the first potential virulence marker of the influenza A(H1N1)pdm09 virus that was associated with severe clinical outcomes. The vast majority of influenza A(H1N1)pdm2009 viruses tested by the WHO-GISRS (World Health Organization-Global Influenza Surveillance and Response System) laboratories were sensitive to neuraminidase inhibitor (NAI) drugs, and during the 2011–2012 influenza season the resistance prevalence was low (1%) or undetectable in the United States and Europe. Resistance to NAIs was detected predominantly in patients with severe conditions, most of whom were immunosuppressed. The resistance was usually associated with the H275Y mutation in the NA protein sequence, although other amino acid substitutions were also reported to confer resistance or decreased susceptibility to 1 or more NAIs. Global virological surveillance should be strengthened for new influenza variants carrying new mutations or reassorted segments that may affect viral features such as virulence, transmission, or antiviral susceptibility.

It might even explain why the flu-shot is aparently inefective.