Mixed infection and the genesis of influenza virus diversity.
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.
Ghedin
Elodie
E
University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, Pennsylvania 15261, USA. elg21@pitt.edu
Fitch
Adam
A
Boyne
Alex
A
Griesemer
Sara
S
DePasse
Jay
J
Bera
Jayati
J
Zhang
Xu
X
Halpin
Rebecca A
RA
Smit
Marita
M
Jennings
Lance
L
St George
Kirsten
K
Holmes
Edward C
EC
Spiro
David J
DJ
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