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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Virus and Prion Research » Research » Publications at this Location » Publication #361841

Research Project: Intervention Strategies to Control Influenza A Virus Infection in Swine

Location: Virus and Prion Research

Title: Molecular determinants facilitating sustained interspecies transmission of human H3N2 influenza A virus in United States pigs

Author
item POWELL, JOSHUA - Oak Ridge Institute For Science And Education (ORISE)
item Abente, Eugenio
item SOUZA, CARINE - Oak Ridge Institute For Science And Education (ORISE)
item CHANG, JENNIFER - Oak Ridge Institute For Science And Education (ORISE)
item RAJAO, DANIELLA - University Of Georgia
item Anderson, Tavis
item Vincent, Amy

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/17/2019
Publication Date: 6/24/2019
Citation: Powell, J.D., Abente, E.J., Souza, C.K., Chang, J., Rajao, D.S., Anderson, T.K., Vincent, A.L. 2019. Molecular determinants facilitating sustained interspecies transmission of human H3N2 influenza A virus in United States pigs [abstract]. Centers of Excellence Influenza Research and Surveillance (CEIRS) meeting. p. none assigned.

Interpretive Summary:

Technical Abstract: Influenza A viruses (IAV) are repeatedly exchanged between humans and pigs, but only a small fraction of these become established and are subsequently transmitted in the new host population. A recent example of human-to-swine transmission is a group of H3N2 viruses possessing a human seasonal H3N2 derived hemagglutinin (HA) that was first detected in 2012 by USDA surveillance. These viruses reassorted with endemic swine IAV, displayed sustained transmission, are now currently the dominant H3 HA gene detected in US pigs, and named the 2010.1 H3 clade to differentiate from the previous endemic H3. Using the first swine H3.2010.1 virus isolated, a closely related human seasonal H3N2 virus as a putative “founder” virus, and additional 2010.1 H3 viruses detected in swine, we studied the evolution of these viruses as they continue to persist in the swine population. We identified four conserved HA amino acid mutations in field-sourced 2010.1 strains (n=632) that were distinct from human seasonal H3 (T135A, T140K, N225D, and G510E). Using site-directed mutagenesis in various in vitro assays and in vivo animal studies, we evaluated the role of these four HA amino acids in the adaptation of human H3 to swine. We found that residue 140 was important in facilitating increased hemagglutinin receptor binding avidity. Residue 135 was important in increased resistance to surfactant protein D neutralization, while residue 510 was important in increasing virion stability (thermal stability- HA assay). Additionally, swine-associated mutations at 135, 140, 225 and 510 allowed for increased replication in porcine respiratory cells. These results provide insight into the molecular role these HA residues played in enabling 2010.1 viruses to adapt in pigs.