Deep sequencing reveals mixed infection with 2009 pandemic influenza A (H1N1) virus strains and the emergence of oseltamivir resistance

Elodie Ghedin, Jennifer Laplante, Jay DePasse, David E. Wentworth, Roberto P. Santos, Martha L. Lepow, Joanne Porter, Kathleen Stellrecht, Xudong Lin, Darwin Operario, Sara Griesemer, Adam Fitch, Rebecca A. Halpin, Timothy B. Stockwell, David J. Spiro, Edward C. Holmes, Kirsten St George

Research output: Contribution to journalArticle

Abstract

Mixed infections with seasonal influenza A virus strains are a common occurrence and an important source of genetic diversity. Prolonged viral shedding, as observed in immunocompromised individuals, can lead to mutational accumulation over extended periods. Recently, drug resistance was reported in immunosuppressed patients infected with the 2009 pandemic influenza A (H1N1) virus within a few days after oseltamivir treatment was initiated. To better understand the evolution and emergence of drug resistance in these circumstances, we used a deep sequencing approach to survey the viral population from an immunosuppressed patient infected with H1N1/2009 influenza and treated with neuraminidase inhibitors. This patient harbored 3 genetic variants from 2 phylogenetically distinct viral clades of pandemic H1N1/2009, strongly suggestive of mixed infection. Strikingly, one of these variants also developed drug resistance de novo in response to oseltamivir treatment. Immunocompromised individuals may, therefore, constitute an important source of genetic and phenotypic diversity, both through mixed infection and de novo mutation.

Original languageEnglish (US)
Pages (from-to)168-174
Number of pages7
JournalJournal of Infectious Diseases
Volume203
Issue number2
DOIs
StatePublished - Jan 15 2011

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Oseltamivir
High-Throughput Nucleotide Sequencing
H1N1 Subtype Influenza A Virus
Influenza A virus
Pandemics
Coinfection
Drug Resistance
Virus Shedding
Neuraminidase
Human Influenza
Mutation
Therapeutics
Population

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Deep sequencing reveals mixed infection with 2009 pandemic influenza A (H1N1) virus strains and the emergence of oseltamivir resistance. / Ghedin, Elodie; Laplante, Jennifer; DePasse, Jay; Wentworth, David E.; Santos, Roberto P.; Lepow, Martha L.; Porter, Joanne; Stellrecht, Kathleen; Lin, Xudong; Operario, Darwin; Griesemer, Sara; Fitch, Adam; Halpin, Rebecca A.; Stockwell, Timothy B.; Spiro, David J.; Holmes, Edward C.; St George, Kirsten.

In: Journal of Infectious Diseases, Vol. 203, No. 2, 15.01.2011, p. 168-174.

Research output: Contribution to journalArticle

Ghedin, E, Laplante, J, DePasse, J, Wentworth, DE, Santos, RP, Lepow, ML, Porter, J, Stellrecht, K, Lin, X, Operario, D, Griesemer, S, Fitch, A, Halpin, RA, Stockwell, TB, Spiro, DJ, Holmes, EC & St George, K 2011, 'Deep sequencing reveals mixed infection with 2009 pandemic influenza A (H1N1) virus strains and the emergence of oseltamivir resistance', Journal of Infectious Diseases, vol. 203, no. 2, pp. 168-174. https://doi.org/10.1093/infdis/jiq040
Ghedin, Elodie ; Laplante, Jennifer ; DePasse, Jay ; Wentworth, David E. ; Santos, Roberto P. ; Lepow, Martha L. ; Porter, Joanne ; Stellrecht, Kathleen ; Lin, Xudong ; Operario, Darwin ; Griesemer, Sara ; Fitch, Adam ; Halpin, Rebecca A. ; Stockwell, Timothy B. ; Spiro, David J. ; Holmes, Edward C. ; St George, Kirsten. / Deep sequencing reveals mixed infection with 2009 pandemic influenza A (H1N1) virus strains and the emergence of oseltamivir resistance. In: Journal of Infectious Diseases. 2011 ; Vol. 203, No. 2. pp. 168-174.
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