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Nat Commun . Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and n

tetano

Editor, Senior Moderator
Nat Commun


. 2025 Jul 1;16(1):5738.
doi: 10.1038/s41467-025-60407-y. Highly pathogenic avian influenza H5N1 clade 2.3.4.4b genotype B3.13 is highly virulent for mice, rapidly causing acute pulmonary and neurologic disease

Thomas Tipih[SUP] 1 [/SUP], Vignesh Mariappan[SUP] 1 [/SUP], Kwe C Yinda[SUP] 1 [/SUP], Kimberly Meade-White[SUP] 1 [/SUP], Matthew Lewis[SUP] 1 [/SUP], Atsushi Okumura[SUP] 1 [/SUP], Natalie McCarthy[SUP] 1 [/SUP], Ekaterina Altynova[SUP] 1 [/SUP], Shanna S Leventhal[SUP] 1 [/SUP], Trenton Bushmaker[SUP] 1 [/SUP], Chad S Clancy[SUP] 2 [/SUP], Emmie de Wit[SUP] 1 [/SUP], Vincent J Munster[SUP] 1 [/SUP], Heinz Feldmann[SUP] 3 [/SUP], Kyle Rosenke[SUP] 4 [/SUP]



Affiliations
Abstract

The highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b viruses, responsible for the current outbreak in dairy cows in the United States, pose a significant animal and public health threat. In this study, we compare disease progression and pathology of three recent clade 2.3.4.4b isolates derived from a cow, a mountain lion, and a mink to a human HPAI A(H5N1) isolate from Vietnam in mice. Inoculating C57BL/6J and BALB/c mice with all four HPAI A(H5N1) isolates results in comparable levels of virus replication in the lung inducing significant local pro-inflammatory cytokine responses and severe respiratory disease. Infecting C57BL/6J mice with the bovine isolate yields high viral titers in the brain, a significant pro-inflammatory cytokine response and neurologic disease. Our findings suggest the recent bovine isolate possesses enhanced neuroinvasive/neurovirulent disease causing fatal respiratory and neurologic disease in C57BL/6J mice.


 
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