Spatiotemporal reconstruction of the North American A(H5N1) outbreak reveals successive lineage replacements by descendant reassortants
Anthony V. Signore, Jolene A. Giacinti, Megan Jones, Cassidy N. G. Erdelyan, Angela McLaughlin, Tamiru N. Alkie, Sherri Cox, Stéphane Lair, Claire M. Jardine, Brian Stevens, Maria Bravo-Araya, Neil Pople, Margo J. Pybus, Tamiko Hisanaga, Wanhong Xu, Janice Koziuk, Oliver Lung, Peter Kruczkiewicz, Mathew Fisher, Jordan Wight, Ishraq Rahman, Kathryn E. Hargan, Andrew S. Lang, Orie Hochman, Davor Ojkić, Carmencita Yason, British Columbia Wildlife AIV Surveillance Program, Laura Bourque, Trent K. Bollinger, Jennifer F. Provencher, Sarah Ogilvie, Amanda Clark, Robyn MacPhee, Hazel Eaglesome, Sayrah Gilbert, Kelsey Saboraki, Richard Davis, Alexandra Jerao, Matthew Ginn, Catherine Soos, Yohannes Berhane
Abstract
The November 2021 introduction of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b into North America triggered a devastating outbreak, affecting more than 180 million domestic birds and spreading to more than 80 wildlife species across Canada and the US. From this outbreak, we have sequenced 2955 complete A(H5N1) viral genomes from samples collected in Canada and, in conjunction with previously published data, performed multifaceted phylodynamic analyses. These analyses reveal extensive diversification of A(H5N1) viruses via reassortment with low-pathogenic avian influenza viruses. We find evidence of repeated ancestral strain replacement by direct descendants, indicative of compounding viral fitness increases. Spatiotemporal modeling identified critical geographic areas facilitating transcontinental spread and demonstrated genotype-specific host dynamics, offering essential data for ongoing control and prevention strategies.