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Avian influenza in cattle - H5N1 virus replication is limited to the udder

Press Releases

Study in Nature clarifies open questions

Insel Riems, 25.09.2024 - Since March 2024, a massive outbreak of avian influenza of the highly pathogenic subtype H5N1 in cattle in the USA has caused considerable problems for the local dairy industry. A study published in Nature provides answers about the behavior of these viruses in cattle, the sites of virus replication, and probable routes of transmission.

The first reports of this unusual outbreak describe a decline in milk yield, virus multiplication in the udder and high excretion rates in the milk. As of September 2024, more than 200 dairy farms in 14 US states have been affected, with additional farms testing positive regularly being added to the list. In addition, 15 human infections with the bovine-associated avian influenza virus have been confirmed to date (four of which were directly linked to contact with infected cattle or their milk). However, many questions were still unanswered or only poorly supported by data: Can the American bovine H5N1 virus of clade 2.3.4.4b, genotype B3.13 also replicate in the respiratory tract? Can European avian influenza viruses of subtype H5N1 also multiply in the udder? How severe is the disease in cattle, how long is the virus excreted in the milk and does it spread systemically in the individual animal?

A group of researchers from the FLI on the island of Riems, together with researchers from Kansas State University (KSU) in Kansas, USA, have now been able to answer these questions by means of two independent, experimental infection trials in lactating cows (FLI) and calves (KSU). The FLI was able to show that a direct H5N1 infection of the udder led to severe symptoms, sometimes with high fever and mastitis, regardless of whether the virus isolate used originated from the USA or Europe. Very high virus loads were detected in the milk of all infected cows and milk production decreased rapidly. However, neither nasal virus replication nor systemic spread was observed throughout the body of the infected cows. In contrast to the already cattle-adapted bovine strain from the USA, a single mammalian adaptation was detected very early in a viral protein of the European H5N1 isolate responsible for virus replication (polymerase PB2 E627K substitution).

The KSU researchers were able to show that an oronasal H5N1 infection of calves with the US strain resulted in only moderate virus replication in the respiratory tract and that the virus was not transmitted to contact calves. 

These two important animal studies allow us to conclude that, in addition to the American H5N1 variant, other H5N1 viruses of clade 2.3.4.4b are also able to replicate efficiently in the bovine udder tissue and are excreted in high quantities in the milk.”, says the head of the study at the FLI, Prof. Dr. Martin Beer, Head of the Institute of Virus Diagnostics and Vice President of the FLI. “It is also very clear that in the USA, milk and milking procedures are primarily responsible for the spread and transmission between dairy cows, rather than the respiratory route.

Both research teams conclude with an urgent call for immediate, effective and comprehensive measures to stop the ongoing spread in cattle in the USA as quickly as possible, to prevent further genetic adaptations of the virus and thereby prevent further transmission to poultry, wild birds and other mammals, including humans.

The study was published in the prestigious journal “Nature” on 25.09.2024: https://www.nature.com/articles/s41586-024-08063-y

This work was funded by the ‘KAPPA-FLU’ project (Horizon Europe programme, project no. 101084171) and the ‘DURABLE’ project, co-financed by the European Union (EU4Health programme, project no. 101102733) and the BMBF project ‘PREPMEDVET’ (project no. 13N15449).

Cow, milking

Cow, milking (© Pixabay)