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

TitlePresence of oseltamivir-resistant pandemic A/H1N1 minor variants before drug therapy with subsequent selection and transmission.
Publication TypeJournal Article
Year of Publication2012
AuthorsGhedin E, Holmes EC, DePasse JV, Pinilla LTatiana, Fitch A, Hamelin M-E, Papenburg J, Boivin G
JournalJ Infect Dis
Volume206
Issue10
Pagination1504-11
Date Published2012 Nov 15
ISSN1537-6613
KeywordsAdolescent, Antiviral Agents, Child, Preschool, Drug Resistance, Viral, Humans, Influenza A Virus, H1N1 Subtype, Influenza, Human, Male, Middle Aged, Neuraminidase, Oseltamivir, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, RNA, Viral, Zanamivir
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.

DOI10.1093/infdis/jis571
Alternate JournalJ. Infect. Dis.
PubMed ID22966122
PubMed Central IDPMC3475640
Grant List2R01 GM080533-06 / GM / NIGMS NIH HHS / United States
U54 GM088491 / GM / NIGMS NIH HHS / United States
U54 GM088491 / GM / NIGMS NIH HHS / United States
/ / Canadian Institutes of Health Research / Canada
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