title: Influenza A virus transmission bottlenecks are defined by infection route and recipient host.
abstract: Despite its global relevance, our understanding of how influenza A virus transmission impacts the overall population dynamics of this RNA virus remains incomplete. To define this dynamic, we inserted neutral barcodes into the influenza A virus genome to generate a population of viruses that can be individually tracked during transmission events. We find that physiological bottlenecks differ dramatically based on the infection route and level of adaptation required for efficient replication. Strong genetic pressures are responsible for bottlenecks during adaptation across different host species, whereas transmission between susceptible hosts results in bottlenecks that are not genetically driven and occur at the level of the recipient. Additionally, the infection route significantly influences the bottleneck stringency, with aerosol transmission imposing greater selection than direct contact. These transmission constraints have implications in understanding the global migration of virus populations and provide a clearer perspective on the emergence of pandemic strains.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Varble
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Backes
authors.affiliation: The Laboratory of Biophysics, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Marshall
authors.initials: M
authors.lastname: Crumiller
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Bouvier
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: benjamin.tenoever@mssm.edu.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: tenOever
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058893:DNA Barcoding, Taxonomic; D018562:Disease Transmission, Infectious / Q000662:veterinary; D004285:Dogs; D005289:Ferrets; D016679:Genome, Viral; D006168:Guinea Pigs; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000472:pathogenicity*; D007251:Influenza, Human / Q000635:transmission*; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D009976:Orthomyxoviridae Infections / Q000635:transmission*