Seibert, B. A.; Parish, M. A.; Talukdar, S. N.; Zhang, T.; Chaulagain, S.; Liu, J. A.; Sachithanandham, J.; Schneider, C.; Coughlan, L.; Bowman, A.; Webby, R. J.; Harkema, J. R.; Pekosz, A.; Klein, S. L.

Panzootic spillover of H5N1 virus clade 2.3.4.4b has resulted in expanded host range among placental mammals, with lactation transmission via milk documented. Whether infection during pregnancy leads to in utero or lactational vertical transmission remains unknown. Pregnant outbred mice were infected with A/bovine/Ohio/B24OSU-472/2024 during the second or third trimester equivalent. Second trimester infection caused in utero infection, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection resulted in offspring with decreased size and neurodevelopmental delays, with infectious virus detected in the neonatal milk ring and lungs as well as mammary tissues. Ongoing H5N1 infections present increased risk for human exposure and an H5N1 vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.