Article information
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.
Keywords:
Surveillance
Resistance
Vaccine
Oseltamivir
H275Y
Resumen
El virus de la gripe A(H1N1)pdm09 ha estado evolucionando continuamente desde abril de 2009 hasta la actualidad. Los cambios experimentados en los aminoácidos del virus pueden alterar sus características antigénicas, su virulencia y su sensibilidad a los fármacos antivirales. Mediante el análisis filogenético del gen hemaglutinina (HA) del virus A(H1N1)pdm09 se han observado 8 grupos genéticos relacionados con el A/California/7/2009, además de otros informados por las redes regionales de vigilancia de la gripe, si bien ninguno de estos grupos genéticos ha sido considerado antigénicamente distinto del virus de la vacuna A/California/7/2009, cuyo uso se recomendó durante la estación de gripe 2012–2013 en el hemisferio norte. El primer marcador de virulencia potencial del virus de la gripe A(H1N1)pdm09 que fue asociado con una mayor severidad clínica de la enfermedad fue la sustitución del aminoácido D222G en la subunidad HA1 del HA. La inmensa mayoría de los virus de la gripe A(H1N1)pdm2009 estudiados por los laboratorios del WHO-GISRS (World Health Organization-Global Influenza Surveillance and Response System) eran sensibles a los fármacos inhibidores de la neuraminidasa (INA). Tanto en Estados Unidos como en Europa, el predominio de resistencia fue bajo (1%) o indetectable durante la temporada de gripe 2011–2012. Los pacientes con enfermedad grave, la mayoría de los cuales eran inmunodeprimidos, fueron principalmente los que presentaron resistencia a los INA. Habitualmente, la resistencia estaba asociada a la mutación de H275Y en la secuencia de la proteína NA, aunque también se apreciaron otras sustituciones de aminoácido que conferían resistencia o disminución de la sensibilidad a uno o más INA. Los autores recomiendan extremar la vigilancia virológica global para detectar nuevas variantes de la gripe debidas a nuevas mutaciones o reordenamientos genómicos que pueden afectar características virales como la virulencia, la transmisión o la sensibilidad a los antivirales.
Palabras clave:
Vigilancia
Resistencia
Vacuna
Oseltamivir
H275Y
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