TY - JOUR
T1 - Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance
AU - Frise, Rebecca
AU - Bradley, Konrad
AU - Van Doremalen, Neeltje
AU - Galiano, Monica
AU - Elderfield, Ruth A.
AU - Stilwell, Peter
AU - Ashcroft, Jonathan W.
AU - Fernandez-Alonso, Mirian
AU - Miah, Shahjahan
AU - Lackenby, Angie
AU - Roberts, Kim L.
AU - Donnelly, Christl A.
AU - Barclay, Wendy S.
PY - 2016/7/19
Y1 - 2016/7/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84979031854&partnerID=8YFLogxK
U2 - 10.1038/srep29793
DO - 10.1038/srep29793
M3 - Article
C2 - 27430528
AN - SCOPUS:84979031854
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 29793
ER -