Antiviral susceptibility of highly pathogenic avian influenza A(H5N1) viruses isolated from poultry, Vietnam, 2009-2011

Emerg Infect Dis. 2013 Dec;19(12):1963-71. doi: 10.3201/eid1912.130705.

Abstract

We assessed drug susceptibilities of 125 avian influenza A(H5N1) viruses isolated from poultry in Vietnam during 2009-2011. Of 25 clade 1.1 viruses, all possessed a marker of resistance to M2 blockers amantadine and rimantadine; 24 were inhibited by neuraminidase inhibitors. One clade 1.1 virus contained the R430W neuraminidase gene and reduced inhibition by oseltamivir, zanamivir, and laninamivir 12-, 73-, and 29-fold, respectively. Three of 30 clade 2.3.4 viruses contained a I223T mutation and showed 7-fold reduced inhibition by oseltamivir. One of 70 clade 2.3.2.1 viruses had the H275Y marker of oseltamivir resistance and exhibited highly reduced inhibition by oseltamivir and peramivir; antiviral agents DAS181 and favipiravir inhibited H275Y mutant virus replication in MDCK-SIAT1 cells. Replicative fitness of the H275Y mutant virus was comparable to that of wildtype virus. These findings highlight the role of drug susceptibility monitoring of H5N1 subtype viruses circulating among birds to inform antiviral stockpiling decisions for pandemic preparedness.

Keywords: H275Y; H5N1; Influenza; Oseltamivir; antiviral; viruses; zoonoses.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Drug Resistance, Viral
  • Ferrets
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Influenza A Virus, H5N1 Subtype / drug effects*
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / isolation & purification
  • Influenza in Birds / epidemiology*
  • Influenza in Birds / virology*
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Mutation
  • Neuraminidase / genetics
  • Neuraminidase / metabolism
  • Oseltamivir / pharmacology
  • Phylogeny
  • Poultry / virology
  • Public Health Surveillance
  • Vietnam / epidemiology
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Oseltamivir
  • Neuraminidase