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Title:   Author  item
                                            NELSON, MARTHA - Fogarty International Centeritem
                                            Baker, Amyitem
                                            Kitikoon, Pravinaitem
                                            HOLMES, EDWARD - Pennsylvania State Universityitem
                                            GRAMER, MARIE - University Of Minnesota
  Submitted to: Journal of Virology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/6/2012
                                    Publication  Date: 8/1/2012
                                    Citation: Nelson, M.I., Vincent, A.L., Kitikoon, P., Holmes, E.C., Gramer, M.R. 2012. The evolution of novel reassortant A/H3N2 influenza viruses in North American swine and humans, 2009-2011. Journal of Virology. 86(16):8872-8878.Interpretive Summary: This study investigated the genetic evolution of novel reassortant swine influenza A viruses detected in the United States and Canada 2009-2011, with a focus on H3N2 influenza viruses. Also included in the analyses were the A(H3N2)v viruses with swine influenza virus genetic lineage that infected 12 humans in the United States since July 2011. The A(H3N2)v is antigenically distinct from the contemporary H3N2 circulating in humans and included in the human trivalent vaccine, and hence represents a potential pandemic threat. Our analysis revealed that novel H3N2 swine viruses have been generated by approximately 4-10 reassortment events in North American swine during 2009-2011 that involve the pandemic matrix (M) gene segment and the hemagglutinin (HA) and neuraminidase (NA) surface protein genes of endemic A/H3N2 swine influenza viruses. The pandemic M segment has also reassorted with other A/H1N1 viruses that are endemic in North American swine, disseminating a segment throughout the swine population that has been associated with aerosol transmission in ferrets, guinea pigs, and now possibly in humans. We also determined that all 12 A(H3N2)v viruses isolated from humans contain a swine N2 segment that was acquired via reassortment with seasonal human influenza viruses from 2001-2002 after the original 1998 emergence of the triple reassortant H3N2 in swine. The identification of this N2 segment may have implications for adaptation to the human host as well as implications for vaccine design due to lack of pre-existing immunity in humans of different age groups. Monitoring and reporting the evolutionary dynamics of the critical H3, N2, and pandemic M gene segments in swine at a detailed level is required to understand how these novel H3N2 viruses emerged in swine, to identify key experimental studies for the future, and to assess the potential epidemic and/or pandemic threat posed to humans.
                                Technical Abstract: Novel H3N2 influenza viruses (H3N2v) containing seven genome segments from swine-lineage triple reassortant H3N2 viruses and a 2009 pandemic H1N1 (H1N1pdm09) matrix protein segment (pM) have been isolated from 12 humans in the United States between August – December 2011. To understand the evolution of these novel H3N2 viruses in swine and humans, we undertook a phylogenetic analysis of 674 M sequences and 388 HA and NA sequences from influenza viruses isolated from North American swine during 2009-2011, as well as HA, NA, and M sequences from eight H3N2v viruses isolated from humans. We identified 34 swine influenza viruses (termed rH3N2p) with the same combination of H3, N2, and pM segments as the H3N2v viruses isolated from humans. Notably, these rH3N2p viruses were generated in swine via reassortment events between H3N2 viruses and the pM segment approximately 4 - 10 times since 2009. The pM segment has also reassorted with multiple antigenically distinct H1 viruses, especially H1' viruses. Importantly, the N2 segment of all H3N2v viruses isolated from humans is derived from a genetically distinct N2 lineage that has circulated in swine since acquired by reassortment with seasonal human H3N2 viruses in 2001-2002, rather than from the N2 that is associated with the 1998 H3N2 swine lineage. The identification of this N2 variant likely has implications for influenza vaccine design and the potential pandemic threat of H3N2v to human age groups with differing levels of prior exposure and immunity.


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