H5N1 clade 2.3.4.4b dynamics in experimentally infected calves and cows

Authors: HALWE, NICO JOEL - Friedrich-Loeffler-institut; COOL, KONNER - Kansas State University; BREITHAUPT, ANGELE - Friedrich-Loeffler-institut; SCHON, JACOB - Friedrich-Loeffler-institute; TRUJILLO, JESSIE - Kansas State University; NOORUZZAMAN, MOHAMMED - Cornell University; KWON, TAEYONG - Kansas State University; AHRENS, ANNE KATHRIN - Friedrich-Loeffler-institut; BRITZKE, TOBIAS - Kansas State University; MCDOWELL, CHESTER - Kansas State University; PIESCHE, RONJA - Friedrich-Loeffler-institut; SINGH, GAGANDEEP - Kansas State University; PINHO DOS REIS, VINICIUS - Friedrich-Loeffler-institut; KAFLE, SUJAN - Kansas State University; POHLMANN, ANNE - Friedrich-Loeffler-institut; GAUDREAULT, NATASHA - Kansas State University; CORLEIS, BJORN - Friedrich-Loeffler-institute; MATIAS-FERREYRA, FRANCO - Kansas State University; CAROSSINO, MARIANO - Louisiana State University; BALASURIYA, UDENI B.R. - Louisiana State University; Hensley, Lisa; MOROZOV, IGOR - Kansas State University; COVALEDA, LINA - Cornell University; DIEL, DIEGO - Cornell University; ULRICH, LORENZ - Friedrich-Loeffler-institut; HOFFMANN, DONATA - Friedrich-Loeffler-institut; BEER, MARTIN - Friedrich-Loeffler-institut; RICHT, JUERGEN - Kansas State University

Submitted to: Nature
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/17/2024
Publication Date: 9/25/2024
Citation: Halwe, N., Cool, K., Breithaupt, A., Schon, J., Trujillo, J., Nooruzzaman, M., Kwon, T., Ahrens, A., Britzke, T., Mcdowell, C.D., Piesche, R., Singh, G., Pinho Dos Reis, V., Kafle, S., Pohlmann, A., Gaudreault, N.N., Corleis, B., Matias-Ferreyra, F.S., Carossino, M., Balasuriya, U., Hensley, L.E., Morozov, I., Covaleda, L.M., Diel, D., Ulrich, L., Hoffmann, D., Beer, M., Richt, J.A. 2024. H5N1 clade 2.3.4.4b dynamics in experimentally infected calves and cows. Nature. https://doi.org/10.1038/s41586-024-08063-y.
DOI: https://doi.org/10.1038/s41586-024-08063-y

Interpretive Summary: This paper explored if calves and dairy cattle could be infected by highly pathogenic avian influenza virus (HPAIV) circulating in the dairy farms in the United States or with a strain circulating in wild birds in Europe. The paper showed that calves and dairy cattle could be infected. Infected dairy cows showed reduced milk production. In addition, the isolate from European wild birds showed adaptation indicating that other strains of highly pathogenic avian influenza virus (HPAIV) may have the potential to cause disease in dairy cows.

Technical Abstract: In March 2024, highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b H5N1 infections in dairy cows were first reported from Texas, USA. Rapid dissemination to more than 170 farms in 13 states followed. Here, we provide results of two independent clade 2.3.4.4b experimental infection studies evaluating: (i) oronasal susceptibility and transmission in calves of a US genotype B3.13 H5N1 isolate and (ii) direct mammary gland inoculation of the US genotype B3.13 H5N1 isolate and a current European wild bird strain of clade 2.3.4.4b into lactating cows. Inoculation of the calves resulted in a mild infection with moderate nasal replication and shedding with no obvious clinical signs or transmission to sentinel calves. In dairy cows, no nasal shedding, but severe acute mammary gland infection with necrotizing mastitis and high fever was observed for both strains. Milk production was drastically reduced and the general condition of the cows was severely compromised. Virus titers in milk rapidly peaked at 108 TCID50/mL, but systemic infection did not ensue. Notably, adaptive mutation PB2 E627K emerged after intramammary replication of the European isolate. Our data suggest that in addition to US genotype B3.13, other HPAIV H5N1 strains have potential to replicate in the udder of cows and that respiratory spread is unlikely the primary mode of H5N1 transmission between cattle.