Abstract Title
Pathogenesis and Pandemic Potential: Differential Cell Death Induction by Diverse Influenza A Viruses from Avian, Swine, and Human Hosts
Abstract
Programmed cell death (PCD) (apoptosis, pyroptosis, and/or necroptosis) is a hallmark of viral infections. Apoptosis is non-inflammatory, while pyroptosis and necroptosis are lytic and inflammatory. PCD induced by low-pathogenic IAV subtypes from non-human hosts is uncharacterized and comparison of human IAV isolates from different time points is lacking. Two avian IAVs, an H1N2 from a murre and an H13N6 from a gull, two swine IAVs, a H1N1 and a H3N2, and eight human IAVs (H1N1s and H3N2s from varying places and years) were cultured in MDCK and A549 cells, with infection and PCD examination. Lytic death was quantified by LDH release and probes and/or antibodies allowed visualization of PCD and viral proteins. Avian and swine viruses induced varied but substantial LDH release. The avian viruses displayed differential PCD with the H13N6 virus inducing primarily pyroptosis while the H1N2 virus induced primarily necroptosis. Surprisingly, the H13N6 virus was capable of productively infecting human lung cells, while the H1N2 virus caused abortive infections. The swine viruses displayed similar patterns of PCD although differed in magnitude. Investigation of human viruses is ongoing and expected to reveal differential PCD induction. We found preferential PCD induction by avian and swine IAVs and report H13 infection of human lung cells. This work characterizes pathogenesis of IAVs from non-human hosts and will include important comparisons to human viruses. Importantly, this work may also give insight into spillover potential and pathogenesis of IAVs, as the threat of influenza outbreaks remains an ever-present concern to both humans and animals.
Co-Author(s)
Hannah L. Wallace*1,2, Jordan Wight 1,3,4, Cassandra L. Gardner 2, Davor Ojkic 5, Andrew S. Lang 3, Rodney S. Russell 2, Jason Kindrachuk 1,6,7
*Presenting Author
Author Affiliations:
1 Medical Microbiology & Infectious Diseases Department, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
2 Immunology and Infectious Diseases, Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John’s, NL, Canada
3 Department of Biology, Faculty of Science, Memorial University, St. John’s, NL, Canada
4 Special Pathogens Program, National Microbiology Laboratory Branch, Public Health Agency of Canada, Winnipeg, MB, Canada
5 Animal Health Laboratory, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
6 Manitoba Centre for Proteomics and Systems Biology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
7 Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health