Location: Virus and Prion ResearchTitle: The growing diversity of H3N2 influenza A virus in swine and the impact on control in swine and at the human animal interface
Submitted to: Proceedings of Allen D Leman Swine Conference
Publication Type: Proceedings
Publication Acceptance Date: 7/12/2013
Publication Date: 9/14/2013
Citation: Vincent, A.L., Kitikoon, P., Anderson, T.K., Loving, C.L. 2013. The growing diversity of H3N2 influenza A virus in swine and the impact on control in swine and at the human animal interface. Proceedings of the 2013 Allen D Leman Swine Conference. p. 161-63.
Technical Abstract: Introduction. H3N2 influenza A viruses (IAV) were recognized as endemic infections in the USA swine population following the 1997-98 incursion of the triple reassortant viruses with gene segments from human- (HA, NA, and PB1), swine- (NP, M, and NS) and avian- (PB2 and PA) adapted viruses (reviewed in ). The significance of the constellation of triple reassortant internal genes (TRIG) would be realized from that critical turning point into the present day, during which time we have observed the TRIG viruses reassort numerous times to acquire new surface genes (beta-, gamma-, delta1-, and delta2-H1N1 and H1N2; H2N3) in the USA, to be exported to new regions (China and South Korea for example), as well as to donate genes to the first human pandemic virus of the 21st century, H1N1pdm09 . Concurrent with frequent reassortment has been a dramatic evolution of IAV in swine in the USA, resulting in multiple antigenic variants that co-circulate and severely challenge our control measures. Recently, efforts within the public and animal health sectors to increase monitoring of IAV in populations of interest have been implemented, with the ultimate goals of improved detection and control interventions. The public health efforts are linked to a mandate instituted in 2005, requiring all human cases of infection with novel influenza viruses be reported to the World Health Organization under the International Health Regulations. Consequently, investment in resources for domestic detection and reporting mechanisms for novel IAV in humans has increased. This includes all zoonotic infections of humans with swine IAV, termed "variant" IAV and denoted by a lower case "v" following the subtype. On the animal health side, the USDA implemented a swine influenza surveillance system in 2009 in response to the growing concern over endemic swine IAV and the emergence of the H1N1pdm09 and subsequent spillover from humans to pigs in the USA. Data from both sectors have provided invaluable insights into the nature of IAV adapted to swine and the implications of spillover that occurs in both directions between humans and pigs. Although sporadic infection of humans with H1N1 and H1N2 swine IAV were reported since 2005, none have occurred with the magnitude of the recent H3N2v cases , thus H3N2 in swine and H3N2v in humans will be the primary focus of this presentation. Evolution of IAV in swine. Recent improvements in influenza surveillance in swine populations in the USA allow for timely epidemiologic, phylogenetic, and virologic analyses that monitor emergence of novel viruses and assess changes in viral population dynamics. A phylogenetic analysis was conducted on sequences from IAV isolated from U.S. swine during 2009–2012 through voluntary and anonymous submissions into the USDA IAV swine surveillance system (T. K. Anderson, submitted). These analyses revealed changes in population dynamics among multiple clades of H1N1, H3N2, and H1N2 co-circulating in U.S. swine populations during 2009-2012. Viral isolates were categorized into one of seven genetically and antigenically distinct hemagglutinin (HA) lineages: H1alpha, H1beta, H1gamma, H1delta1, H1delta2, H1pdm09 and H3 cluster IV. Over this period there was a dramatic increase in occurrence of H1d1 in samples submitted, with a concurrent decrease in H1pdm09. H3 cluster-IV exhibited increasing diversification, with multiple distinct phylogenetic branches emerging and being sustained since 2010 [4, 5]. Although H3N2 represented 25% of identified viruses, this subtype was reported in increasing proportion of sequenced isolates since late 2011. In addition to the phylogenetic clusters of H3, at least 10 distinct reassorted H3N2/H1N1pdm09 (rH3N2p) genotypes were identified in studies at NADC  and by others [6, 7]. Nearly all of the H3N2 reassortants characterized in the USA contain the matrix gen