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Title:   Author  item
                                            NELSON, MARTHA - Fogarty International Centeritem
                                            WENTWORTH, DAVID - J Craig Venter Instituteitem
                                            CULHANE, MARIE - Minnesota Veterinary Diagnostic Laboratoriesitem
                                            Baker, Amyitem
                                            VIBOUD, CECILE - Fogarty International Centeritem
                                            LAPOINTE, MATTHEW - J Craig Venter Instituteitem
                                            LIN, XUDONG - J Craig Venter Instituteitem
                                            HOLMES, EDWARD - University Of Sydneyitem
                                            DETMER, SUSAN - University Of Saskatchewan
  Submitted to: Journal of Virology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/16/2014
                                    Publication  Date: 9/1/2014
                                    Citation: Nelson, M.I., Wentworth, D.E., Culhane, M.R., Vincent, A.L., Viboud, C., LaPointe, M.P., Lin, X., Holmes, E.C., Detmer, S.E. 2014. Introductions and evolution of human-origin seasonal influenza A viruses in multinational swine populations. Journal of Virology. 88(17):10110-10119.Interpretive Summary: The swine origin of the 2009 A/H1N1 pandemic virus underscored the importance of understanding how influenza A virus (IAV) evolves in swine. While the importance of swine in the evolution of IAV and potential for human infection with swine viruses is well documented, the role of human-to-swine transmission has not been as intensively studied. Through a large-scale sequencing effort we identified a novel influenza virus of wholly human origin that has been circulating undetected in swine for at least seven years. In addition, we demonstrate that human-to-swine transmission has occurred extremely frequently at a global scale over the past decades, with the major viral proteins hemagglutinin and neuraminidase being maintained in swine. This has greatly contributed to the diversity of IAV in swine world wide. However, there is little persistence of the other human virus gene segments in swine, suggesting there are requirements for successful introduction and maintenance of human viruses in swine. These findings are central to understanding the complex biology of influenza and the disease threats that swine and humans pose to each other.
                                Technical Abstract: The capacity of influenza A viruses to cross species barriers presents a continual threat to human and animal health.  Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. We sequenced the genomes of 141 influenza viruses collected from North American swine during 2002-2011 and identified a swine virus that possessed all eight genome segments of human seasonal A/H3N2 virus origin. A molecular clock analysis indicates that this virus – A/sw/Saskatchewan/02903/2009(H3N2) – has likely circulated undetected in swine for at least seven years. For historical context, we performed a comprehensive phylogenetic analysis of an additional 1,404 whole-genome sequences from swine influenza A viruses collected globally during 1931-2013. Human-to-swine transmission occurred frequently over this time period, with 20 discrete introductions of human seasonal influenza A viruses showing sustained onward transmission in swine for at least one year since 1965. Notably, human-origin hemagglutinin (H1 and H3) and neuraminidase (particularly N2) segments were detected in swine at a much higher rate than the six internal gene segments, indicating that most human viruses adapt to new swine hosts by acquiring swine-origin internal genes via reassortment. Further understanding of the fitness constraints on the adaptation of human viruses to swine, and vice versa, at a genomic level is central to understanding the complex multi-host ecology of influenza and the disease threats that swine and humans pose to each other.


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