Location: Virus and Prion Research
Project Number: 5030-32000-120-007-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Aug 1, 2015
End Date: Jul 31, 2020
Objective:
Utilize hemagglutination inhibition assays with the ARS reference serum panel, antigenic cartography and sequence analysis tools to quantify swine influenza A virus evolution in Brazil.
Approach:
Swine have long been hypothesized to be a mixing vessel for potential pandemic influenza A viruses (IAV) and were the source of the 2009 H1N1 human pandemic virus. However, more recent data have revealed the interconnectedness between human seasonal and endemic swine IAV and the dramatic impact that human IAV incursion into swine populations has had in shaping the complex evolution of swine IAV. Although there is marked genetic heterogeneity recognized among swine H1N1, H1N2, and H3N2 viruses circulating in pigs globally, there is limited publically available data from Brazil, despite having the world's third largest swine population at 41 million head. In addition, the antigenic diversity among current swine influenza viruses and their relationship to human seasonal influenza strains is relatively poorly characterized. The goal of this research is to use advanced phylogenetic analyses, protein modeling, and antigenic cartography resources to further characterize IAV from swine in Brazil. This work supports the objective to quantify genetic and antigenic evolution of IAV in swine, their relationships to human seasonal viruses, and population immunity in both host species to assess interspecies transmission risk and to develop rational vaccine approaches in swine. Data from recent swine surveillance activities in Brazil have indicated previously unappreciated genetic diversity in swine IAV as well as human-to-swine incursions. Since 2009, H1N1pdm09, H1N2 and H3N2 IAVs have been isolated from pigs. The phylogenetic analyses performed so far of 16 IAVs revealed the introduction and circulation in swine of three lineages of human seasonal virus that have not been previously observed in any other country. These swine viruses have reassorted with the H1N1pdm09 in Brazil, further increasing genetic diversity. An additional 78 isolates were collected from 2010-2014 that have not yet been sequenced and none of the isolates have been antigenically characterized by the ARS reference panel and antigenic cartography. Since nucleotide and amino acid sequences alone may not accurately define the antigenic property of a virus (single amino acid changes in the HA protein can result in loss of antibody recognition), it is necessary to incorporate multiple approaches to assess significant change. Computational tools to quantify and visualize the data are critical as the data sets become more complex. USDA will provide sequence analysis support and the ARS H1 and H3 antisera panels, reference viruses and sequences. The use of a common set of sera that includes current human seasonal viruses will allow incorporation of the Brazilian swine viruses for a global understanding of the antigenic diversity of swine IAV. We will collaborate with the University of Cambridge to use antigenic cartography to quantify the evolution of swine influenza viruses in pigs from Brazil and their relationship to current and previously circulating human influenza virus strains.
