Influenza A virus field surveillance at a swine-human interface

Authors: RAMBO-MARTIN, BENJAMIN - Battelle Memorial Institute; KELLER, MATTHEW - Oak Ridge Institute For Science And Education (ORISE); WILSON, MALANIA - Battelle Memorial Institute; NOLTING, JACQUELINE - The Ohio State University; Anderson, Tavis; Baker, Amy; BAGAL, UJWAL - Battelle Memorial Institute; JANG, YUNHO - Battelle Memorial Institute; NEUHAUS, ELIZABETH - Centers For Disease Control And Prevention (CDC) - United States; DAVIS, C - Centers For Disease Control And Prevention (CDC) - United States; BOWMAN, ANDREW - The Ohio State University; WENTWORTH, DAVID - Centers For Disease Control And Prevention (CDC) - United States; BARNES, JOHN - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: mSphere
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/14/2020
Publication Date: 2/20/2020
Citation: Rambo-Martin, B.L., Keller, M.W., Wilson, M.M., Nolting, J.M., Anderson, T.K., Vincent, A.L., Bagal, U., Jang, Y., Neuhaus, E.B., Davis, C.T., Bowman, A.A., Wentworth, D.E., Barnes, J.R. 2020. Influenza A virus field surveillance at a swine-human interface. mSphere. 5(1):e00822-19. https://doi.org/10.1128/mSphere.00822-19.
DOI: https://doi.org/10.1128/mSphere.00822-19

Interpretive Summary: Influenza A virus (IAV) is an important pathogen of swine and humans. Swine and humans can share some strains of IAV, and swine IAV can lead to sporadic human infection, called "variant" IAV in humans. These variant transmission events are often associated with animal agricultural exhibits and swine exposure. ARS scientists collaborated with public and animal health researchers to develop and deploy a rapid and mobile sequencing method for identifying and characterizing IAV detected in pigs at a public swine exhibit. Using this technology on-site at the exhibit, 13 virus genomes from infected swine were sequenced and characterized within 18 hours, dramatically reducing time to diagnosis and allowing time for intervention and mitigation of further transmission to other swine and/or humans in contact with the infected pigs on-site. This information also informs vaccine strain selection for swine and for humans as part of pandemic preparedness.

Technical Abstract: We developed and deployed a rapid and portable Influenza A virus (IAV) sequencing and analysis pipeline we call Mia (Mobile Influenza Analysis). Working overnight at a large swine exhibition, we nanopore-sequenced the IAV genomes collected from 24 swine. We identified an IAV outbreak and determined in real-time that it posed a novel risk to the human population due to the found viruses’ differences to current candidate vaccine viruses (CVV). This is the first report of field-derived nanopore sequencing data yielding a real-time, actionable public health response. Exhibition swine are a known source for zoonotic transmission of influenza A viruses (IAV) to humans and pose a potential pandemic risk. Genomic analyses of IAV in exhibition swine are critical to understanding this risk, the types of viruses circulating in exhibits and whether current vaccines developed for use in humans would be predicted to provide immune protection. We completed full-length consensus sequences of 13 virus genomes roughly 18 hours after unpacking the lab. Automated, on-site analyses of the data identified one gamma lineage A(H1N1), one human-like A(H3N2), and 11 highly similar delta-2 lineage A(H1N2) IAVs. Additional analysis of the HA protein sequences of the A(H1N2) viruses showed more than 20 amino acid differences compared to previously developed pre-pandemic CVVs at numerous sites predicted to affect antigenicity. With the current CVVs being predicted to lack coverage against the outbreak viruses, all virus sequences were emailed to collaborators who initiated development of a synthetically derived CVV.