title: Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance.
abstract: Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution.
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Frise
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Konrad
authors.initials: K
authors.lastname: Bradley
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Neeltje
authors.initials: N
authors.lastname: van Doremalen
authors.affiliation: Public Health England, Colindale, London, United Kingdom.
authors.forename: Monica
authors.initials: M
authors.lastname: Galiano
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Elderfield
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Stilwell
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Ashcroft
authors.affiliation: Public Health England, Colindale, London, United Kingdom.
authors.forename: Mirian
authors.initials: M
authors.lastname: Fernandez-Alonso
authors.affiliation: Public Health England, Colindale, London, United Kingdom.
authors.forename: Shahjahan
authors.initials: S
authors.lastname: Miah
authors.affiliation: Public Health England, Colindale, London, United Kingdom.
authors.forename: Angie
authors.initials: A
authors.lastname: Lackenby
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Roberts
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Faculty of Medicine, Imperial College London, United Kingdom.
authors.forename: Christl A
authors.initials: CA
authors.lastname: Donnelly
authors.affiliation: Imperial College London, Faculty of Medicine, Division of Infectious Disease, Norfolk Place, London, W2 1PG, United Kingdom.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Barclay
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D018562:Disease Transmission, Infectious; D004285:Dogs; D024882:Drug Resistance, Viral; D005260:Female; D005289:Ferrets; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D007251:Influenza, Human / Q000635:transmission / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000517:prevention & control / Q000635:transmission* / Q000821:virology; D053139:Oseltamivir / Q000494:pharmacology; D012137:Respiratory System / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D053139:Oseltamivir