title: Mixed infection and the genesis of influenza virus diversity.
abstract: 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.
authors: University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, Pennsylvania 15261, USA. elg21@pitt.edu
authors: Elodie
authors: E
authors: Ghedin
authors: Adam
authors: A
authors: Fitch
authors: Alex
authors: A
authors: Boyne
authors: Sara
authors: S
authors: Griesemer
authors: Jay
authors: J
authors: DePasse
authors: Jayati
authors: J
authors: Bera
authors: Xu
authors: X
authors: Zhang
authors: Rebecca A
authors: RA
authors: Halpin
authors: Marita
authors: M
authors: Smit
authors: Lance
authors: L
authors: Jennings
authors: Kirsten
authors: K
authors: St George
authors: Edward C
authors: EC
authors: Holmes
authors: David J
authors: DJ
authors: Spiro
mesh_terms: D016000:Cluster Analysis; D015897:Comorbidity; D019143:Evolution, Molecular; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000302:isolation & purification; D009981:Influenza B virus / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology* / Q000821:virology*; D008969:Molecular Sequence Data; D016865:Reassortant Viruses; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology