Mammalian Adaptation of an Avian-Like Influenza Virus
We are especially excited to share our new publication, appearing as the featured article in Cell Host & Microbe, on the evolution of H1N1 influenza during infection. Our study traces the genetics of the virus as it progresses during the infection of a single individual, and as it transmits to new individuals, using ferrets as a host. Interestingly, we find that numerous virus particles found the first infection, when it transfers to the new host. This is presumably because the virus has not yet adapted to the new host species. However, when the infection later spreads to other individuals, relatively few viral particles found new infections. The reason for this may be that a single round of infection is enough time for the virus to adapt appreciably to the new species, and the new adapted viruses are able to out-compete all other virus particles when founding the new infection. We further verify previous findings suggesting that specific mutations in hemagglutinin (the ‘H’ in H1N1) are responsible for the ability to successfully infect new hosts, with the caveat that several such mutations will do the trick. To learn more, read the abstract and full study below!
ABSTRACT:
Avian influenza virus reassortants resembling the 1918 human pandemic virus can become transmissible among mammals by acquiring mutations in hemagglutinin (HA)and polymerase. Using the ferret model, we trace the evolutionary pathway by which an avian-like virus evolves the capacity for mammalian replication and airborne transmission. During initial infection, within-host HA diversity increased drastically. Then, airborne transmission fixed two polymerase mutations that do not confer a detectable replication advantage. In later transmissions, selection fixed advantageous HA1 variants. Transmission initially involved a ‘‘loose’’ bottleneck, which became strongly selective after additional HA mutations emerged. The stringency and evolutionary forces governing between-host bottlenecks may therefore change throughout host adaptation. Mutations occurred in multiple combinations in transmitted viruses, suggesting that mammalian transmissibility can evolve through multiple genetic pathways despite phenotypic constraints. Our data provide a glimpse into avian influenza virus adaptation in mammals, with broad implications for surveillance on potentially zoonotic viruses.
FULL STUDY:
Moncla LH, Zhong G, Nelson CW, Dinis JM, Mutschler J, Hughes AL, Watanabe T, Kawaoka Y, Friedrich TC [2016] Selective bottlenecks shape evolutionary pathways taken during mammalian adaptation of a 1918-like avian influenza virus. Cell Host & Microbe 19(2):169-80.