A cow resting in her stall. In the foreground is a colorized transmission electron micrograph of H5N1 virus particles (yellow). In 2024, H5N1 chook flu has been inflicting outbreaks in poultry and U.S. dairy cows. Cow photograph by NIAID; micrograph, which has been repositioned and recolored by NIAID, is courtesy CDC. Credit: NIAID and CDC
Research on H5N1 influenza in U.S. dairy cattle exhibits the virus could cause extreme illness in mice and ferrets however lacks environment friendly transmission by respiratory droplets. This discovering suggests a restricted potential for these bovine-derived viruses to trigger widespread illness amongst mammals.
Experimental Findings From H5N1 Infection in U.S. Dairy Cattle
A collection of experiments with extremely pathogenic H5N1 avian influenza (HPAI H5N1) viruses circulating in contaminated U.S. dairy cattle discovered that viruses derived from lactating dairy cattle induced extreme illness in mice and ferrets when administered through intranasal inoculation. The virus from the H5N1-infected cows certain to each avian (chook) and human-type mobile receptors, however, importantly, didn’t transmit effectively amongst ferrets uncovered through respiratory droplets.
The findings, revealed on July 8 in the journal Nature, recommend that bovine (cow) HPAI H5N1 viruses might differ from earlier HPAI H5N1 viruses and that these viruses might possess options that would facilitate an infection and transmission amongst mammals. However, they at the moment don’t seem succesful of environment friendly respiratory transmission between animals or folks.
In March 2024, an outbreak of HPAI H5N1 was reported amongst U.S. dairy cattle which unfold throughout herds and led to deadly infections amongst some cats on affected farms, spillover into poultry, and 4 reported infections amongst dairy staff. The HPAI H5N1 viruses remoted from affected cattle are intently associated to H5N1 viruses which have circulated in North American wild birds since late 2021. Over time, these avian viruses have undergone genetic adjustments and have unfold all through the continent inflicting outbreaks in wild birds and mammals—typically with mortality charges and suspected transmission inside species.
Colorized transmission electron micrograph of avian influenza A H5N1 virus particles (yellow/purple), grown in Madin-Darby Canine Kidney (MDCK) epithelial cells. Microscopy by CDC; repositioned and recolored by NIAID. Credit: CDC and NIAID
Research Methods and Animal Model Results
To higher perceive the traits of the bovine H5N1 viruses, researchers from the University of Wisconsin-Madison, Japan’s Shizuoka and Tokyo Universities, and Texas A&M Veterinary Medical Diagnostic Laboratory carried out experiments to decide the capacity of bovine HPAI H5N1 to replicate and trigger illness in mice and ferrets, that are routinely used for influenza A virus research. Ferrets are thought to be mannequin for understanding potential influenza transmission patterns in folks as a result of they exhibit related medical signs, immune responses and develop respiratory tract infections like people.
The researchers intranasally administered to mice doses of bovine HPAI H5N1 influenza of growing strength (5 mice per dosage group), after which monitored the animals for body weight adjustments and survival for 15 days. All the mice that acquired the greater doses died of an infection. Some of the mice that acquired decrease doses survived, and those who acquired the lowest dose skilled no body weight loss and survived.
Comparative Studies and Transmission Tests
The researchers additionally in contrast the results of the bovine HPAI H5N1 virus to a Vietnamese H5N1 pressure that’s typical of H5N1 avian influenza virus in people and to an H1N1 influenza virus, each delivered intranasally to mice. The mice that acquired both the bovine HPAI H5N1 virus or the Vietnamese avian H5N1 virus skilled high virus ranges in respiratory and non-respiratory organs, together with in the mammary glands and muscle tissues, and sporadic detection in the eyes. The H1N1 virus was discovered solely in the respiratory tissues of the animals.
Ferrets intranasally contaminated with the bovine HPAI H5N1 virus skilled elevated temperatures and loss of body weight. As with the mice, the scientists found high virus ranges in the ferrets’ higher and decrease respiratory tracts and different organs. Unlike the mice, nevertheless, no virus was present in the ferrets’ blood or muscle tissues.
“Together, our pathogenicity studies in mice and ferrets revealed that HPAI H5N1 derived from lactating dairy cattle may induce severe disease after oral ingestion or respiratory infection, and infection by either the oral or respiratory route can lead to systemic spread of virus to non-respiratory tissues including the eye, mammary gland, teat and/or muscle,” the authors write.
To take a look at whether or not bovine H5N1 viruses transmit amongst mammals through respiratory droplets, reminiscent of emitted by coughs and sneezes, the researchers contaminated teams of ferrets (4 animals per group) with both bovine HPAI H5N1 virus or H1N1 influenza, which is understood to transmit effectively through respiratory droplets. One day later, uninfected ferrets had been housed in cages subsequent to the contaminated animals. Ferrets contaminated with both of the influenza viruses confirmed medical indicators of illness and high virus ranges in nasal swabs collected over a number of days. However, solely ferrets uncovered to the H1N1-infected group confirmed indicators of medical illness, indicating that the cow influenza virus doesn’t transmit effectively through respiratory droplets in ferrets.
Typically, avian and human influenza A viruses don’t connect to the similar receptors on cell surfaces to provoke an infection. The researchers discovered, nevertheless, that the bovine HPAI H5N1 viruses can bind to each, elevating the chance that the virus might have the capacity to bind to cells in the higher respiratory tract of people.
“Collectively, our study demonstrates that bovine H5N1 viruses may differ from previously circulating HPAI H5N1 viruses by possessing dual human/avian-type receptor-binding specificity with limited respiratory droplet transmission in ferrets,” the authors stated.
Reference: “Pathogenicity and transmissibility of bovine H5N1 influenza virus” by Amie J. Eisfeld, Asim Biswas, Lizheng Guan, Chunyang Gu, Tadashi Maemura, Sanja Trifkovic, Tong Wang, Lavanya Babujee, Randall Dahn, Peter J. Halfmann, Tera Barnhardt, Gabriele Neumann, Yasuo Suzuki, Alexis Thompson, Amy Okay. Swinford, Kiril M. Dimitrov, Keith Poulsen and Yoshihiro Kawaoka, 8 July 2024, Nature.
DOI: 10.1038/s41586-024-07766-6
The National Institute of Allergy and Infectious Diseases (NIAID), half of the National Institutes of Health, funded the work of the University of Wisconsin-Madison researchers.
