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Antiviral Res ; 83(1): 90-3, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19501261

RESUMEN

The neuraminidase inhibitors (NAIs) are an effective class of antiviral drugs for the treatment of influenza A and B infections. Until recently, only a low prevalence of NAI resistance (<1%) had been detected in circulating viruses. However, surveillance in Europe in late 2007 revealed significant numbers of A(H1N1) influenza strains with a H274Y neuraminidase mutation that were highly resistant to the NAI oseltamivir. We examined 264 A(H1N1) viruses collected in 2008 from South Africa, Oceania and SE Asia for their susceptibility to NAIs oseltamivir, zanamivir and peramivir in a fluorescence-based neuraminidase inhibition assay. Viruses with reduced oseltamivir susceptibility were further analysed by pyrosequencing assay. The frequency of the oseltamivir-resistant H274Y mutant increased significantly after May 2008, resulting in an overall proportion of 64% (168/264) resistance among A(H1N1) strains, although this subtype represented only 11.6% of all isolates received during 2008. H274Y mutant viruses demonstrated on average a 1466-fold reduction in oseltamivir susceptibility and 527-fold reduction in peramivir sensitivity compared to wild-type A(H1N1) viruses. The mutation had no impact on zanamivir susceptibility. Ongoing surveillance is essential to monitor how these strains may spread or persist in the future and to evaluate the effectiveness of treatments against them.


Asunto(s)
Antivirales/farmacología , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/virología , Oseltamivir/farmacología , Ácidos Carbocíclicos , Sustitución de Aminoácidos/genética , Asia Sudoriental , Análisis por Conglomerados , Ciclopentanos/farmacología , Guanidinas/farmacología , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Mutación Missense , Neuraminidasa/genética , Neuraminidasa/metabolismo , Oceanía , Filogenia , ARN Viral/genética , Análisis de Secuencia de ADN , Homología de Secuencia , Sudáfrica , Proteínas Virales/genética , Proteínas Virales/metabolismo , Zanamivir/farmacología
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