Abstract
Influenza viruses exist in each host as a collection of genetically diverse variants, which might enhance their adaptive potential. To assess the genetic and functional diversity of highly pathogenic avian influenza A(H5N1) viruses within infected humans, we used deep-sequencing methods to characterize samples obtained from infected patients in northern Vietnam during 2004–2010 on different days after infection, from different anatomic sites, or both. We detected changes in virus genes that affected receptor binding, polymerase activity, or interferon antagonism, suggesting that these factors could play roles in influenza virus adaptation to humans. However, the frequency of most of these mutations remained low in the samples tested, implying that they were not efficiently selected within these hosts. Our data suggest that adaptation of influenza A(H5N1) viruses is probably stepwise and depends on accumulating combinations of mutations that alter function while maintaining fitness.
Highlights
Influenza viruses exist in each host as a collection of genetically diverse variants, which might enhance their adaptive potential
We recently found that selection pressure on hemagglutinin (HA) can impose a strong population bottleneck during virus transmission: a variant representing only 5.9% of the total virus population in animals infected with a reassortant influenza A(H5N1) virus infected an animal via aerosol transmission [11]
We only considered single-nucleotide polymorphisms (SNPs) present in >1% of sequence reads within a population; we previously showed that this stringent cutoff excludes false-positive SNPs generated by using our approach [11]
Summary
Influenza viruses exist in each host as a collection of genetically diverse variants, which might enhance their adaptive potential. To assess the genetic and functional diversity of highly pathogenic avian influenza A(H5N1) viruses within infected humans, we used deep-sequencing methods to characterize samples obtained from infected patients in northern Vietnam during 2004–2010 on different days after infection, from different anatomic sites, or both. We recently found that selection pressure on hemagglutinin (HA) can impose a strong population bottleneck during virus transmission: a variant representing only 5.9% of the total virus population in animals infected with a reassortant influenza A(H5N1) virus infected an animal via aerosol transmission [11]. These findings prompted us to seek a deeper understanding of virus populations in infected humans. We used deep-sequencing and functional analyses to evaluate the genetic and functional diversity among influenza A(H5N1) viruses in infected humans
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