Pathogenesis of bovine H5N1 clade 2.3.4.4b infection in macaques

Kyle Rosenke, Amanda Griffin, Franziska Kaiser, Ekaterina Altynova, Reshma Mukesh, Trenton Bushmaker, Meaghan Flagg, Thomas Tipih, Kerry Goldin, Arthur Wickenhagen, Brandi N. Williamson, Shane Gallogly, Shanna S. Leventhal, Tessa Lutterman, Atsushi Okumura, Matthew C. Lewis, Kishore Kanakabandi, Craig Martens, Kwe C. Yinda, Deepashri Rao, Brian J. Smith, Carl Shaia, Greg Saturday, Patrick Hanley, Neeltje Doremalen, Emmie Wit (), Vincent J. Munster () and Heinz Feldmann ()
Additional contact information
Kyle Rosenke: Rocky Mountain Laboratories
Amanda Griffin: Rocky Mountain Laboratories
Franziska Kaiser: Rocky Mountain Laboratories
Ekaterina Altynova: Rocky Mountain Laboratories
Reshma Mukesh: Rocky Mountain Laboratories
Trenton Bushmaker: Rocky Mountain Laboratories
Meaghan Flagg: Rocky Mountain Laboratories
Thomas Tipih: Rocky Mountain Laboratories
Kerry Goldin: Rocky Mountain Laboratories
Arthur Wickenhagen: Rocky Mountain Laboratories
Brandi N. Williamson: Rocky Mountain Laboratories
Shane Gallogly: Rocky Mountain Laboratories
Shanna S. Leventhal: Rocky Mountain Laboratories
Tessa Lutterman: Rocky Mountain Laboratories
Atsushi Okumura: Rocky Mountain Laboratories
Matthew C. Lewis: Rocky Mountain Laboratories
Kishore Kanakabandi: Rocky Mountain Laboratories
Craig Martens: Rocky Mountain Laboratories
Kwe C. Yinda: Rocky Mountain Laboratories
Deepashri Rao: Rocky Mountain Laboratories
Brian J. Smith: Rocky Mountain Laboratories
Carl Shaia: Rocky Mountain Laboratories
Greg Saturday: Rocky Mountain Laboratories
Patrick Hanley: Rocky Mountain Laboratories
Neeltje Doremalen: Rocky Mountain Laboratories
Emmie Wit: Rocky Mountain Laboratories
Vincent J. Munster: Rocky Mountain Laboratories
Heinz Feldmann: Rocky Mountain Laboratories

Nature, 2025, vol. 640, issue 8060, 1017-1021

Abstract: Abstract Since early 2022, highly pathogenic avian influenza (HPAI) H5N1 virus infections have been reported in wild aquatic birds and poultry throughout the USA with spillover into several mammalian species1–6. In March 2024, HPAIV H5N1 clade 2.3.4.4b was first detected in dairy cows in Texas, USA, and continues to circulate on dairy farms in many states7,8. Milk production and quality are diminished in infected dairy cows, with high virus titres in milk raising concerns of exposure to mammals including humans through consumption9–12. Here we investigated routes of infection with bovine HPAIV H5N1 clade 2.3.4.4b in cynomolgus macaques, a surrogate model for human infection13. We show that intranasal or intratracheal inoculation of macaques could cause systemic infection resulting in mild and severe respiratory disease, respectively. By contrast, infection by the orogastric route resulted in limited infection and seroconversion of macaques that remained subclinical.

Date: 2025
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DOI: 10.1038/s41586-025-08609-8

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