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2533365 
Journal Article 
Influenza A Virus Transmission Bottlenecks Are Defined by Infection Route and Recipient Host 
Varble, A; Albrecht, RA; Backes, S; Crumiller, M; Bouvier, NM; Sachs, D; García-Sastre, A; Tenoever, BR 
2014 
Yes 
Cell Host and Microbe
ISSN: 1931-3128 
CELL PRESS 
CAMBRIDGE 
16 
5 
691-700 
English 
25456074 
WOS:000345123900018 
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.