Media Advisory
Monday July 8, 2024
The H5N1 virus was not transmitted efficiently by the respiratory route to ferrets.
What
A series of experiments with highly pathogenic avian influenza H5N1 (HPAI H5N1) viruses circulating in infected dairy cows in the United States revealed that viruses derived from lactating dairy cows caused severe disease in mice and ferrets when administered by intranasal inoculation. Virus from H5N1-infected cows bound to both avian (bird) and human-type cellular receptors but, importantly, did not transmit efficiently among ferrets exposed by respiratory droplets. The results, published in Naturesuggest that bovine (cow) HPAI H5N1 viruses may differ from previous HPAI H5N1 viruses and that these viruses may possess characteristics that may facilitate infection and transmission between mammals. However, they do not currently appear capable of efficient respiratory transmission between animals or humans.
In March 2024, an outbreak of highly pathogenic avian influenza (HPAI) type H5N1 was reported among U.S. dairy cows. It spread throughout herds, resulting in fatal infections in some cats on affected farms, contamination in poultry, and four infections reported among dairy workers. The HPAI H5N1 viruses isolated from affected cattle are closely related to H5N1 viruses that have been circulating in wild birds in North America since late 2021. Over time, these avian viruses have undergone genetic changes and spread across the continent, causing outbreaks in wild birds and mammals, sometimes with mortality rates and suspected intraspecies transmission.
To better understand the characteristics of bovine H5N1 viruses, researchers from the University of Wisconsin-Madison, the Universities of Shizuoka and Tokyo in Japan, and the Texas A&M Veterinary Medical Diagnostic Laboratory conducted experiments to determine the ability of bovine H5N1 HPAI virus to replicate and cause disease in mice and ferrets, which are routinely used for influenza A virus studies. Ferrets are considered a good model for understanding potential patterns of influenza transmission in humans because they have similar clinical symptoms and immune responses and develop respiratory tract infections as humans do.
The researchers intranasally administered increasing doses of HPAI H5N1 bovine influenza virus to mice (5 mice per dose group) and then monitored changes in body weight and survival of the animals for 15 days. All of the mice that received the highest doses died from the infection. Some of the mice that received the lowest doses survived, and those that received the lowest dose did not lose body weight and survived.
The researchers also compared the effects of the bovine H5N1 HPAI virus to those of a Vietnamese H5N1 strain of the human H5N1 avian influenza virus and to those of an H1N1 influenza virus, both administered intranasally to mice. Mice given either the bovine H5N1 HPAI virus or the Vietnamese H5N1 avian virus had high levels of virus in respiratory and nonrespiratory organs, including mammary glands and muscle tissues, and sporadic detection in the eyes. H1N1 virus was detected only in the respiratory tissues of the animals. Ferrets infected intranasally with the bovine H5N1 HPAI virus had elevated temperatures and body weight loss. As in mice, the scientists found high levels of virus in the ferrets’ upper and lower respiratory tracts and other organs. However, unlike mice, no virus was detected in the blood or muscle tissue of ferrets.
“Collectively, our pathogenicity studies in mice and ferrets revealed that HPAI H5N1 virus derived from lactating dairy cows can induce severe disease following oral ingestion or respiratory infection, and that infection via the oral or respiratory route can lead to systemic spread of the virus to non-respiratory tissues, including the eye, mammary gland, teat, and/or muscle,” the authors write.
To test whether bovine H5N1 viruses are transmitted between mammals through respiratory droplets, emitted by coughing and sneezing, the researchers infected groups of ferrets (four animals per group) with either bovine H5N1 HPAI virus or H1N1 influenza virus, which is known to be efficiently transmitted through respiratory droplets. One day later, the uninfected ferrets were placed in cages next to the infected animals. Ferrets infected with either influenza virus showed clinical signs of illness and high levels of virus in nasal swabs collected over several days. However, only ferrets exposed to the H1N1-infected group showed signs of clinical illness, indicating that bovine influenza virus is not efficiently transmitted through respiratory droplets among ferrets.
Typically, avian and human influenza A viruses do not attach to the same receptors on the surface of cells to initiate infection. However, researchers have found that bovine avian influenza H5N1 viruses can bind to both receptors, raising the possibility that the virus may have the ability to bind to cells in the upper respiratory tract of humans.
“Collectively, our study demonstrates that bovine H5N1 viruses may differ from previously circulating HPAI H5N1 viruses by possessing dual human/avian receptor binding specificity with limited respiratory droplet transmission in ferrets,” the authors said.
The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded the work of the University of Wisconsin-Madison researchers.
Article
An Eisfield and othersPathogenicity and transmissibility of bovine influenza virus H5N1 in mice and ferrets. Nature DOI: 10.1038/s41586-024-07766-6 (2024).
WHO
Lauren Byrd-Leotis, Ph.D., of the Viral Respiratory Diseases Section in NIAID’s Division of Microbiology and Infectious Diseases, is available to discuss the findings.
Contact
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