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Title: Genotype patterns of contemporary reassorted H3N2 virus in U.S. swine

item Kitikoon, Pravina
item NELSON, MARTHA - Fogarty International Center
item KILLIAN, MARY LEA - Animal And Plant Health Inspection Service (APHIS)
item Anderson, Tavis
item KOSTER, LEO - Animal And Plant Health Inspection Service (APHIS)
item CULHANE, MARIE - University Of Minnesota
item Baker, Amy

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/6/2013
Publication Date: 6/1/2013
Citation: Kitikoon, P., Nelson, M.I., Killian, M.L., Anderson, T.K., Koster, L., Culhane, M.R., Vincent, A.L. 2013. Genotype patterns of contemporary reassorted H3N2 virus in US swine. Journal of General Virology. 94(Pt 6):1236-1241.

Interpretive Summary: Although it is not uncommon for influenza A viruses found circulating in swine populations to occasionally infect humans, there have been more than 275 swine-origin influenza A viruses (called H3N2v) detected in humans since July 2011 in the United States, with the majority occurring in the summer of 2012. Most of the human cases were detected in people with direct exposure to pigs in various settings, most notably in agricultural fairs. These events underscore the importance of knowing the genetic diversity of influenza viruses circulating in North American swine in order to compare to that of the human H3N2v viruses. Here we performed the largest phylogenetic sequence analysis at a genomic scale of influenza viruses in North American swine to date (n = 200 whole-genome sequences), including 119 swine H3N2 viruses, 67 swine H1N1 viruses, and 14 human H3N2v viruses, collected during 2009-2012. The 119 H3N2 swine viruses comprised two main genomic groups: 55 had standard triple reassortant internal genes (TRIG) found in viruses isolated from North American swine since 1998 and 64 had reassorted with H1N1pdm09 viruses (rH3N2p viruses). All 64 rH3N2p viruses acquired the pandemic M gene segment (M-pdm), and half (n=23) also acquired additional H1N1pdm09 gene segments, representing at least ten distinct rH3N2p genotypes (G1-G10). Importantly, the 7:1 reassortant swine rH3N2p viruses containing the M-pdm gene from H1N1pdm09 (G1) similar to the 2011-2012 H3N2v human cases, were most frequently detected among rH3N2p (n = 23), indicating a possible genetic fitness of this gene combination in swine and a potential for spillover to humans. Although swine G1 viruses appear to have evolved from multiple reassortment events, all human H3N2v viruses available to date clustered within a single G1 clade on the trees inferred for all eight segments, suggesting that the genetic requirements for virus transmission from swine to humans is more stringent than what is observed for transmission among swine. Understanding these requirements may allow prediction of which animal influenza viruses may be of greater risks to humans, aiding in pandemic preparedness.

Technical Abstract: To understand the evolution of H3N2v influenza viruses that have infected 288 humans since July 2011, we performed the largest phylogenetic analysis at a whole genome scale of influenza viruses from North American swine to date (n = 200). At least ten distinct reassorted H3N2/pandemic H1N1 (rH3N2p) genotypes were identified in swine. Genotype 1 (G1) similar to the H3N2v human cases was most frequently detected. All human H3N2v viruses clustered within a single G1 clade, suggesting that the genetic requirements for transmission to humans may be restricted to a specific subset of swine viruses.