BMI/PRISM Combined Seminar Series

Thursday April 2nd

Room: GB06

Time: 11:30 am-12:30 pm

Presenter: Dr. Yan Zhou, PhD. VIDO

"Crossing Species Barriers in Highly Pathogenic Avian Influenza (HPAI) Virus: Pathogenesis, Molecular Adaptation and Immune Evasion”

Influenza A virus infects a wide range of species and poses a persistent threat to both human and animal health. Recently, highly pathogenic avian influenza (HPAI) H5N1 crossed the species barrier and infected the mammary glands of dairy cows, causing mastitis, an abrupt decline in milk production, and viral shedding into milk. More than 70 human HPAI H5N1 infections have been reported, most of which are associated with occupational exposure. This spillover event represents the emergence of a new mammalian host and a novel tissue tropism, highlighting the virus’s capacity to sustain panzootic spread and zoonotic transmission.

We have established multiple animal infection models for HPAI H5N1 virus, including dairy cows, dairy goats and ferrets. Using these models, we demonstrated that intramammary inoculation of dairy cow results in robust viral replication in the mammary gland, recapitulates clinical outcomes observed in the field, and induces protective natural immunity against reinfection. We further showed that dairy goats can serve as a practical surrogate model for studying bovine H5N1 pathogenesis and for vaccine development. At the molecular level, we identified key amino acid determinants in the viral RNA-dependent RNA polymerase that enable efficient replication of avian viruses in mammals and evaluated their contribution to pathogenesis in ferrets. In addition, we demonstrated that the viral NS1 protein functions as a potent interferon antagonist. Together, these findings have important implications for vaccine design and evaluation and advance our understanding of the mechanisms underlying cross-species transmission of HPAI virus.

 

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