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Journal of Virology, September 2009, p. 8832-8841, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00773-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mixed Infection and the Genesis of Influenza Virus Diversity{triangledown}

Elodie Ghedin,1* Adam Fitch,1 Alex Boyne,2 Sara Griesemer,3 Jay DePasse,1 Jayati Bera,2 Xu Zhang,1 Rebecca A. Halpin,2 Marita Smit,4 Lance Jennings,4 Kirsten St. George,3 Edward C. Holmes,5,6 and David J. Spiro2

University of Pittsburgh School of Medicine, Departments of Medicine and Computational Biology, Pittsburgh, Pennsylvania 15261,1 J. Craig Venter Institute, 9704 Medical Center Drive, Rockville, Maryland 20850,2 Wadsworth Center, New York State Department of Health, Albany, New York 12201,3 Canterbury Health Laboratories, Christchurch, New Zealand,4 The Pennsylvania State University, University Park, Pennsylvania 16802,5 Fogarty International Center, National Institutes of Health, Bethesda, Maryland 208926

Received 16 April 2009/ Accepted 16 June 2009

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 to one capable of 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 coinfect the same cells, generating a mixed infection, and then reassort. Determining the nature and frequency of mixed infection with 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 intrahost 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 virus subtype, drug-resistant and -sensitive strains, those that are likely to differ in antigenicity, and even viruses of different influenza virus types (A and B). These results reveal that 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.

* Corresponding author. Mailing address: Division of Infectious Diseases, University of Pittsburgh School of Medicine, 3550 Terrace Street, Room 830, Pittsburgh, PA 15261. Phone: (412) 383-5850. Fax: (412) 383-5851. E-mail: elg21{at}pitt.edu

{triangledown} Published ahead of print on 24 June 2009.

Journal of Virology, September 2009, p. 8832-8841, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00773-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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