Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission

Elodie Ghedin, Edward C. Holmes, Jay V. Depasse, Lady Tatiana Pinilla, Adam Fitch, Marie Eve Hamelin, Jesse Papenburg, Guy Boivin

Research output: Contribution to journalArticle

Abstract

A small proportion (1-1.5) of 2009 pandemic influenza A/H1N1 virus strains (A[H1N1]pdm09) are oseltamivir resistant, almost exclusively because of a H275Y mutation in the neuraminidase protein. However, many individuals infected with resistant strains had not received antivirals. Whether drug-resistant viruses are initially present as minor variants in untreated individuals before they emerge as the dominant strain in a virus population is of great importance for predicting the speed at which resistance will arise. To address this issue, we used ultra-deep sequencing of viral populations from serial nasopharyngeal specimens from an immunocompromised child and from 2 individuals in a household outbreak. We observed that the Y275 mutation was present as a minor variant in infected hosts before the onset of therapy. We also found evidence for the transmission of this drug-resistant variant with drug-susceptible viruses. These observations provide important information on the relative fitness of the Y275 mutation in the absence of oseltamivir treatment.

Original languageEnglish (US)
Pages (from-to)1504-1511
Number of pages8
JournalJournal of Infectious Diseases
Volume206
Issue number10
DOIs
StatePublished - Nov 15 2012

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Oseltamivir
Pandemics
Viruses
Drug Therapy
Mutation
Pharmaceutical Preparations
High-Throughput Nucleotide Sequencing
H1N1 Subtype Influenza A Virus
Influenza A virus
Neuraminidase
Population
Antiviral Agents
Disease Outbreaks
Therapeutics
Proteins

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission. / Ghedin, Elodie; Holmes, Edward C.; Depasse, Jay V.; Pinilla, Lady Tatiana; Fitch, Adam; Hamelin, Marie Eve; Papenburg, Jesse; Boivin, Guy.

In: Journal of Infectious Diseases, Vol. 206, No. 10, 15.11.2012, p. 1504-1511.

Research output: Contribution to journalArticle

Ghedin, Elodie ; Holmes, Edward C. ; Depasse, Jay V. ; Pinilla, Lady Tatiana ; Fitch, Adam ; Hamelin, Marie Eve ; Papenburg, Jesse ; Boivin, Guy. / Presence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission. In: Journal of Infectious Diseases. 2012 ; Vol. 206, No. 10. pp. 1504-1511.
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