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Title: Genetic evolution of recently emerged novel human-like swine H3 influenza A viruses (IAV) in United States swine

Author
item GAUGER, P - Iowa State University
item RAJAO, D - Non ARS Employee
item ANDERSON, T - Orise Fellow
item WALIA, R - Orise Fellow
item LEWIS, N - University Of Cambridge
item ABENTE, E - Orise Fellow
item HARMON, K - Iowa State University
item ZHANG, J - Iowa State University
item Baker, Amy

Submitted to: International Pig Veterinary Society (IPVS)
Publication Type: Abstract Only
Publication Acceptance Date: 3/1/2016
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Introduction Influenza A virus (IAV) is a major cause of respiratory disease in swine. IAV transmission from humans to swine is a major contributor to swine IAV diversity. In 2012, a novel H3N2 with an HA (hu-H3) and NA derived from human seasonal H3N2 was detected in United States (US) swine. The hu-H3 continued to be detected with evidence of reassortment with endemic swine IAV. Swine isolates from 2012 and 2014 with hu-H3 were shown to be fully virulent and transmissible in swine. We conducted a phylogenetic analysis of sixty-eight hu-H3 detected between 2012-15 in the USDA surveillance system and from the Iowa State University Veterinary Diagnostic Laboratory. Materials and Methods Representative whole genome sequences of North American swine and human IAV were compiled with our data. Sequences were aligned and we inferred maximum-likelihood trees in RAxML. Each gene was assigned to an evolutionary lineage (human, classical swine, TRIG, or 2009 pandemic H1N1 (H1pdm09)). A time-scaled Bayesian approach was implemented for the HA gene in BEAST. The deduced HA1 amino acid sequences were used to identify amino acid differences between human and swine viruses. Results An increasing frequency of detection was demonstrated with 3 hu-H3 detected in 2012, 8 in 2013, 17 in 2014, and 40 in 2015. Viruses with the hu-H3 showed at least three reassortment episodes: early viruses contained a human-origin N2; second generation viruses contained a classical swine N1; and third generation viruses contained a swine 2002 N2, with early viruses containing an H1pdm09 backbone and later viruses containing TRIG lineage and H1pdm09 internal genes. The first detection in the USDA swine IAV surveillance system was Nov 2012, but time to the most recent common human H3 ancestor was between Nov 2010 and Feb 2011. These viruses likely went undetected for up to two years, potentially the result of reduced viral replication or transmission in swine during this time. The swine hu-H3 gene differed at up to 25 amino acid positions from closely related human H3, including 8 mutations in recognized antigenic sites. Conclusion Surveillance data demonstrated this novel IAV lineage is established in the U.S. swine population. It spread from detection in a single state in 2012 to 7 states in 2015, with an increasing percentage of isolates in the national surveillance system (3% in 2014; 5% in 2015). These viruses are a significant threat to the industry, as antigenic distance from the swine H3 circulating since 1998 indicates current vaccines will likely have limited efficacy. The risk of transmission of swine IAV with hu-H3 and H1N1pdm09 internal genes back to humans should be considered.