#Pathogenesis of #H5N1 Clade 2.3.4.4b in dry Jersey #cows following intramammary inoculation shows within-host compartmentalization

Abstract

Dairy cattle have emerged as a prolific amplifying host for highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b and a new source for cross-species and zoonotic transmission. Independent introductions of H5N1 with unclear exposure routes have been reported in several dairy herds across the U.S. These events escalate the pandemic potential of HPAIV H5N1 as transmission within and between mammalian species present opportunities for mammalian adapted H5N1 viruses to emerge. Although more than 1000 herds have been infected, bovine H5N1 influenza virus pathogenesis, transmission, and evolution in dairy cattle remains not well characterized. Working with H5N1-infected lactating cattle in high containment has been a major challenge due to the required infrastructure and logistics associated with housing, husbandry, and waste management for this model. Thus, developing alternative bovine models that maintain biological relevance while reducing operational complexity is warranted. Here, we evaluate the susceptibility of lactating Jersey cattle in the dry-off period, and characterize the effect of inoculation dose on the mammary pathogenicity of HPAIV H5N1 genotype B3.13. The results of this study demonstrate that dairy cows 21 days into the dry-off period are highly susceptible to HPAIV H5N1, recapitulating the severe clinical and pathological outcomes observed in infected lactating cows under experimental conditions and in field cases. We also observed an association between virus dose and the onset and severity of mastitis in individual udder-quarters and compartmentalized clonal expansion of variant populations. Overall, this study demonstrates that dry cows can provide a feasible model to study H5N1 virology, pathology, and humoral immunology in dairy cows.

Competing Interest Statement

The J.A.R. laboratory received support from Tonix Pharmaceuticals, Genus plc, Xing Technologies and Zoetis outside of the reported work. J.A.R. is inventor on patents and patent applications, owned by Kansas State University, on the use of antivirals and vaccines for the treatment and prevention of virus infections. The other authors declare no competing interests.

Funder Information Declared

This work was supported by the National Bio and Agro-Defense Facility (NBAF) Transition Fund from the State of Kansas, the USDA Animal Plant Health Inspection Service’s NBAF Scientist Training Program, the AMP and MCB Cores of the Center on Emerging and Zoonotic Infectious Diseases (CEZID) , and the NIAID supported Centers of Excellence for Influenza Research and Response (CEIRR, contract number 75N93021C00016 and subcontract A21-0702-S001). NIGMS. The sequencing infrastructure used in the study was funded by the USDA Animal Plant Health Inspection Services (AP20VSD&B000C086), while sequencing methodology development was funded in part by the USDA National Institute of Food and Agriculture (NIFA) Agriculture and Food Research Initiative (AFRI) (award no. 2021-68014-33635). H.M.M. was supported in part by NIAID T32055397.

Source:

Link: https://www.biorxiv.org/content/10.64898/2026.03.04.709389v1

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#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

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