Eurasian-Origin Gene Segments Contribute to the Transmissibility, Aerosol Release, and Morphology of the 2009 Pandemic H1N1 Influenza Virus

Seema S Lakdawala,Hong Jin,William G Lindsley,Weijia Wang,Yumiko Matsuoka,Celia P Santos,Elaine W Lamirande,Amorsolo L Suguitan,Leatrice Vogel,Kanta Subbarao,Ron A M Fouchier

doi:10.1371/journal.ppat.1002443

Seema S Lakdawala, Hong Jin + Show 9 more

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https://doi.org/10.1371/journal.ppat.1002443

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Abstract

The epidemiological success of pandemic and epidemic influenza A viruses relies on the ability to transmit efficiently from person-to-person via respiratory droplets. Respiratory droplet (RD) transmission of influenza viruses requires efficient replication and release of infectious influenza particles into the air. The 2009 pandemic H1N1 (pH1N1) virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus that contributed the neuraminidase (NA) and M gene segments. Both the TRS and Eurasian swine viruses caused sporadic infections in humans, but failed to spread from person-to-person, unlike the pH1N1 virus. We evaluated the pH1N1 and its precursor viruses in a ferret model to determine the contribution of different viral gene segments on the release of influenza virus particles into the air and on the transmissibility of the pH1N1 virus. We found that the Eurasian-origin gene segments contributed to efficient RD transmission of the pH1N1 virus likely by modulating the release of influenza viral RNA-containing particles into the air. All viruses replicated well in the upper respiratory tract of infected ferrets, suggesting that factors other than viral replication are important for the release of influenza virus particles and transmission. Our studies demonstrate that the release of influenza viral RNA-containing particles into the air correlates with increased NA activity. Additionally, the pleomorphic phenotype of the pH1N1 virus is dependent upon the Eurasian-origin gene segments, suggesting a link between transmission and virus morphology. We have demonstrated that the viruses are released into exhaled air to varying degrees and a constellation of genes influences the transmissibility of the pH1N1 virus.

Highlights

Influenza A viruses pose a global threat to human health
The 2009 pandemic H1N1 virus originated by reassortment of a North American triple reassortant swine (TRS) virus with a Eurasian swine virus
We evaluated the release of influenza viruscontaining aerosols and the transmissibility of the pandemic H1N1 (pH1N1), TRS, and Eurasian viruses in ferrets and found that the Eurasian-origin gene segments contributed to efficient Respiratory droplet (RD) transmission of the pH1N1 virus by modulating the release of influenza viral RNA-containing particles into the air

Summary

Introduction

Influenza A viruses pose a global threat to human health. They circulate in animal hosts and can reassort to generate a virus to which the human population is naıve, creating a potential pandemic threat. Efficient person-to-person transmission of influenza A viruses via RDs is a feature of seasonal epidemics and of pandemics. Determination of the molecular requirements for influenza viruses to transmit efficiently from person-to-person is an essential contribution to our understanding of potential pandemic threats. The animal influenza viruses, avian H5N1, swine H1N1, and swine H1N2 viruses, have sporadically infected humans [4,5,6,7,8] but have not caused an influenza pandemic, presumably because they were unable to transmit efficiently throughout the human population

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