JVI Accepts, published online ahead of print on 24 June 2009

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J. Virol. doi:10.1128/JVI.00773-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mixed Infection and the Genesis of Influenza Diversity

Elodie Ghedin^*, Adam Fitch, Alex Boyne, Sara Griesemer, Jay DePasse, Jayati Bera, Xu Zhang, Rebecca A. Halpin, Marita Smit, Lance Jennings, Kirsten St. George, Edward C. Holmes, and David J. Spiro

University of Pittsburgh School of Medicine, Departments of Medicine and Computational Biology, Pittsburgh, PA 15261, USA; J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, MD 20850, USA; Wadsworth Center, NYSDH, Albany, New York, 12201, USA; Canterbury Health Laboratories, Christchurch, New Zealand; The Pennsylvania State University, University Park, PA 16802, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA

^* To whom correspondence should be addressed. Email: elg21{at}pitt.edu.

The emergence of viral infections with potentially devastating consequences for human health is highly dependent on their underlying evolutionary dynamics. One likely scenario for an avian influenza virus, such as A/H5N1, to evolve human-to-human transmission is through the acquisition of genetic material from the A/H1N1 or A/H3N2 subtypes already circulating in human populations. This would require that viruses of both subtypes co-infect the same cells, generating a mixed infection, and then reassort. Determining the nature and frequency of mixed infection in influenza virus is therefore central to understanding the emergence of pandemic, antigenic and drug resistant strains. To better understand the potential for such events, we explored patterns of intra-host genetic diversity in recently circulating strains of human influenza virus. By analyzing multiple viral genome sequences sampled from individual influenza patients we reveal a high level of mixed infection, including diverse lineages of the same influenza subtype, drug resistant and sensitive strains, those that are likely to differ in antigenicity, and even viruses of different influenza types (A and B). These results reveal individuals can harbor influenza viruses that differ in major phenotypic properties, including those that are antigenically distinct and those that differ in their sensitivity to antiviral agents.