1. Characterization of H5N1 Influenza Virus Quasispecies with Adaptive Hemagglutinin Mutations from Single-Virus Infections of Human Airway Cells
- Author
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Takaaki Nakaya, Emad Mohamed Elgendy, Kazuo Takahashi, Madiha S. Ibrahim, Tatsuo Shioda, Junichi Kajikawa, Kazuhiko Matsumoto, Yasuha Arai, Nongluk Sriwilaijaroen, Takao Ono, Yohei Watanabe, Tatsuya Takagi, Yasuo Suzuki, Norihito Kawashita, Tomo Daidoji, and Hiroaki Hiramatsu
- Subjects
0301 basic medicine ,Respiratory System ,Immunology ,Virus Attachment ,Hemagglutinin Glycoproteins, Influenza Virus ,Respiratory Mucosa ,Viral quasispecies ,Biology ,medicine.disease_cause ,Microbiology ,Virus ,Cell Line ,Madin Darby Canine Kidney Cells ,03 medical and health sciences ,chemistry.chemical_compound ,Dogs ,Virology ,Chlorocebus aethiops ,Influenza, Human ,medicine ,Animals ,Humans ,Vero Cells ,Genetic diversity ,Influenza A Virus, H5N1 Subtype ,Phylogenetic tree ,Genetic Variation ,Lipid bilayer fusion ,respiratory system ,Phenotype ,Influenza A virus subtype H5N1 ,Virus-Cell Interactions ,Sialic acid ,Quasispecies ,HEK293 Cells ,030104 developmental biology ,chemistry ,Insect Science ,Sialic Acids ,Receptors, Virus - Abstract
Transmission of avian influenza (AI) viruses to mammals involves phylogenetic bottlenecks that select small numbers of variants for transmission to new host species. However, little is known about the AI virus quasispecies diversity that produces variants for virus adaptation to humans. Here, we analyzed the hemagglutinin (HA) genetic diversity produced during AI H5N1 single-virus infection of primary human airway cells and characterized the phenotypes of these variants. During single-virus infection, HA variants emerged with increased fitness to infect human cells. These variants generally had decreased HA thermostability, an indicator of decreased transmissibility, that appeared to compensate for their increase in α2,6-linked sialic acid (α2,6 Sia) binding specificity and/or in the membrane fusion pH threshold, each of which is an advantageous mutational change for viral infection of human airway epithelia. An HA variant with increased HA thermostability also emerged but could not outcompete variants with less HA thermostability. These results provided data on HA quasispecies diversity in human airway cells. IMPORTANCE The diversity of the influenza virus quasispecies that emerges from a single infection is the starting point for viral adaptation to new hosts. A few studies have investigated AI virus quasispecies diversity during human adaptation using clinical samples. However, those studies could be appreciably affected by individual variability and multifactorial respiratory factors, which complicate identification of quasispecies diversity produced by selective pressure for increased adaptation to infect human airway cells. Here, we found that detectable HA genetic diversity was produced by H5N1 single-virus infection of human airway cells. Most of the HA variants had increased fitness to infect human airway cells but incurred a fitness cost of less HA stability. To our knowledge, this is the first report to characterize the adaptive changes of AI virus quasispecies produced by infection of human airway cells. These results provide a better perspective on AI virus adaptation to infect humans.
- Published
- 2018