Enhanced encephalitic tropism of bovine H5N1 compared to the Vietnam H5N1 isolate in mice

In recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we inve...

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Bibliographic Details
Published in:bioRxiv 2024-11
Main Authors: Goldin, Kerry, Sarah Van Tol, Johnson, Randall C, Mukesh, Reshma Koolaparambil, Gallogly, Shane, Schulz, Jonathan E, Prado-Smith, Jessica, Saturday, Greg, Kwe Claude Yinda, Munster, Vincent J, De Wit, Emmie, Neeltje Van Doremalen
Format: Article
Language:English
Subjects:
Avian flu
Central nervous system
Choroid plexus
Immunohistochemistry
Infections
Inner ear
Microbiology
Nose
Respiratory diseases
Respiratory tract
Tropism
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Summary:In recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection with either HPAI H5N1 isolate was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Bov342-challenged animals exhibited clinical signs consistent with central nervous system (CNS) infection, and infectious virus was detected in brain tissue. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism, with Bov342 resulting in respiratory disease as well as increased neurotropism and inflammation in the brain and nasal turbinates compared to VN1203, which predominantly induces respiratory disease.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Unintentionally left of an author from the submission form, added in the latest version
ISSN:2692-8205
DOI:10.1101/2024.11.19.624162