93: Bovine H5N1 Shows Neurovirulence in Mice

Tipih T et al., Nature Communications - Comparative mouse study finds a dairy-cow-derived H5N1 clade 2.3.4.4b (genotype B3.13) isolate is highly virulent, producing rapid respiratory failure, systemic spread, and neurologic disease with high lung and brain viral loads and inflammatory responses. Key terms: H5N1, clade 2.3.4.4b, bovine isolate, neuroinvasion, mouse model.

Study Highlights:
Researchers compared bovine, mountain lion, mink and reference VN1203 H5N1 isolates in C57BL/6J and BALB/c mice using intranasal and orogastric inoculation. The bovine isolate caused uniformly lethal, rapid disease and clear neurologic signs in C57BL/6J mice with high lung and brain titers. Brain tissue from bovine-isolate infected mice showed elevated pro-inflammatory cytokines despite limited histologic lesions. BALB/c mice were more susceptible to respiratory disease but showed less neurologic manifestation, indicating strain-dependent outcomes.

Conclusion:
A bovine clade 2.3.4.4b H5N1 isolate (genotype B3.13) demonstrates enhanced neuroinvasion and virulence in mice, supporting the use of C57BL/6J and BALB/c models for countermeasure testing and highlighting the need to monitor mammalian-adapted phenotypes.

Music:
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Article title:
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

First author:
Tipih T

Journal:
Nature Communications

DOI:
10.1038/s41467-025-60407-y

Reference:
Tipih T., Mariaappan V., Yinda K.C., Meade-White K., Lewis M., Okumura A., McCarthy N., Altynova E., Leventhal S.S., Bushmaker T., Clancy C.S., de Wit E., Munster V.J., Feldmann H. & Rosenke K. 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. Nature Communications (2025) 16:5738. DOI: 10.1038/s41467-025-60407-y

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/base-by-base-ep93-h5n1-bovine-neurovirulence

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-08-01.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript's coverage of the article's key experimental design (two mouse strains, two infection routes), main results (bovine isolate virulence, neuroinvasion, brain viral loads, cytokine response, tissue tropism, LD50), genetic determinants (M1/NS1 mutations; absence of PB2 E627K; NA stalk status), and pu
- transcript topics: Background and public health context of H5N1 clade 2.3.4.4b; Experimental design: mouse strains, infection routes, and isolates; Bovine isolate virulence and neuropathogenesis in mice; Brain infection without histological brain lesions and cytokine responses; Tissue tropism and systemic infection (lung, brain, blood); Genetic determinants of virulence (M1/NS1 mutations; PB2 E627K absence; NA stalk; NS1 deletion absence)

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 6
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- articl...