Comparative virulence of wild-type H1N1pdm09 influenza A isolates in swine Jamie N. Henningson a,b,1 , Daniela S. Rajao a,1 , Pravina Kitikoon a,2 , Alessio Lorusso c , Marie R. Culhane d , Nicola S. Lewis e , Tavis K. Anderson a,f , Amy L. Vincent a, * a Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA 50010, USA b Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, K-221 Mosier Hall, Manhattan, KS 66506, USA c Istituto Zooprofilattico Sperimentale dell’Abruzzo e Molise ‘‘G. Caporale’’, Teramo, Italy d University of Minnesota Veterinary Diagnostic Laboratory, 1333 Gortner Avenue, St. Paul, MN 55108, USA e Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK f Department of Biology, Georgia Southern University, P.O. Box 8042-1, Statesboro, GA 30460, USA Veterinary Microbiology xxx (2015) xxx–xxx A R T I C L E I N F O Article history: Received 27 September 2014 Received in revised form 19 December 2014 Accepted 21 December 2014 Keywords: Pandemic Influenza A virus Swine Pathology HI Cross-reactivity A B S T R A C T In 2009, a novel swine-origin H1N1 (H1N1pdm09) influenza A virus (IAV) reached pandemic status and was soon after detected in pigs worldwide. The objective of this study was to evaluate whether differences in the HA protein can affect pathogenicity and antigenicity of H1N1pdm09 in swine. We compared lung pathology, viral replication and shedding and the antigenic relationships of four wild-type H1N1pdm09 viruses in pigs: one human (CA/09) and three isolated in swine after the pandemic (IL/09, IL/10, and MN/10). The swine strains were selected based upon unique amino acid substitutions in the HA protein. All selected viruses resulted in mild disease and viral shedding through nasal and oral fluids, however, viral replication and the degree of pathology varied between the isolates. A/Swine/IL/5265/2010 (IL/10), with substitutions I120M, S146G, S186P, V252M, had lower viral titers in the lungs and nasal secretions and fewer lung lesions. The other two swine viruses caused respiratory pathology and replicated to titers similar to the human CA/09, although MN/10 (with mutations D45Y, K304E, A425S) had lower nasal shedding. Swine-adapted H1N1pdm09 have zoonotic potential, and have reassorted with other co-circulating swine viruses, influencing the evolution of IAV in swine globally. Further, our results suggest that amino acid changes in the HA gene have the potential to alter the virulence of H1N1pdm09 in swine. Importantly, the limited clinical signs in pigs could result in continued circulation of these viruses with other endemic swine IAVs providing opportunities for reassortment. Published by Elsevier B.V. * Corresponding author at: Virus and Prion Research Unit, NADC, USDA-ARS, 1920 Dayton Avenue, PO Box 70, Ames, IA 50010, USA. Tel.: +1 515 337 7557; fax: +1 515 337 7428. E-mail address: amy.vincent@ars.usda.gov (A.L. Vincent). 1 These authors contributed equally to this work. 2 Present address: Merck Animal Health, 35500 W. 91st Street, DeSoto, KS 66018, USA. G Model VETMIC-6856; No. of Pages 10 Please cite this article in press as: Henningson, J.N., et al., Comparative virulence of wild-type H1N1pdm09 influenza ?A isolates in swine. Vet. Microbiol. (2015), http://dx.doi.org/10.1016/j.vetmic.2014.12.021 Contents lists available at ScienceDirect Veterinary Microbiology jo u rn al ho m epag e: ww w.els evier.c o m/lo cat e/vetmic http://dx.doi.org/10.1016/j.vetmic.2014.12.021 0378-1135/Published by Elsevier B.V.