Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep29793
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Funding
- Wellcome Trust [087039/Z/08Z]
- Medical Research Council UK [G0600504]
- NC3Rs grant [NC/K00042X/1]
- UK Medical Research Council
- European Union Seventh Framework Programme [FP7] [nu278433-PREDEMICS]
- National Institute for Health Research Health Protection Research Unit (NIHR HPRU)) in Modelling Methodology at Imperial College London
- Public Health England (PHE)
- Medical Research Council [MR/K010174/1B, G0600504, MR/K010174/1] Funding Source: researchfish
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [NC/K00042X/1] Funding Source: researchfish
- National Institute for Health Research [HPRU-2012-10080] Funding Source: researchfish
- MRC [G0600504, MR/K010174/1] Funding Source: UKRI
- NC3Rs [NC/K00042X/1] Funding Source: UKRI
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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.
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