H5N1 bovine influenza transmitted by an infected worker is transmissible and fatal in animal models

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Antiviral drugs are very effective in treating the H5N1 bovine influenza virus.

Colorized transmission electron microscope of avian influenza A virus H5N1 particles (blue) grown in Madin Darby canine renal epithelial cell cultures. Credit: CDC and NIAID. Credit: CDC and NIAID

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Mice and ferrets that were infected with a highly pathogenic H5N1 avian influenza virus in a laboratory under high-confinement conditions died, according to a recent study. Nature. The researchers found that the same virus, isolated from a worker with mild corneal inflammation (conjunctivitis), can be spread through the air by ferrets separated by some distance. It may also be able to bind and replicate in the respiratory cells of humans.

The worker virus is called huTX37H5N1. It has one mutation, PB2-E627K. This is a common mutation in avian influenza viruses that replicate in mammals. This makes the virus more efficient at replicating. These mutations underscore the importance of continuing to monitor and evaluate viruses in the current H5N1 outbreak.

A strain of bovine H5N1 virus was also susceptible to the antiviral drug favipiravir (brand name Xofluza), as well as to the neuraminidase inhibitor zanamivir. It is also less susceptible to the neuraminidase inhibitor oseltamivir, or Tamiflu.

HuTX37 replicated in human lung and corneal cells in laboratory tests. Scientists determined that the lethal dose of the huTX37 H5N1 virus was less than one plaque-forming unit (PFU) per mouse, compared with 31.6 PFU for a bovine virus of the same name isolated from milk. The huTX37 virus infected 15 mouse tissues, with respiratory tissues having the highest levels of virus.

The researchers also infected ferrets with high doses of huTX37H5N1. Ferret flu is more similar to human flu than mouse flu. The scientists found high levels of huTX37 H5N1 in respiratory tissue, and all infected ferrets died within five days. Researchers had previously infected ferrets with a bovine H5N1 virus. Although it is a serious disease, its lethality is limited.

The scientists placed healthy ferrets 5 cm away from ferrets infected with huTX37 H5N1 at four different doses. The scientists found that all ferrets directly exposed to the virus died within 6 days. Depending on the exposure dose, 17 to 33 % of nearby animals were infected by respiratory droplet spread. The results show that bovine HPAI H5 virus, isolated from an infected person, can be transmitted to mammals by respiratory droplets. However, this is only a limited method.

They note that the infected person did not suffer severe symptoms. Human cases in this outbreak have mostly had conjunctivitis or mild respiratory symptoms. The researchers speculate that a small dose of bovine H5N1 could cause localized conjunctivitis in humans without causing severe disease. They say that multiple exposures to seasonal influenza viruses may provide low-level protection against HPAI H5N1. However, further study is needed.

This study summarizes its findings, which show that the huTX37 H5N1 isolate is pathogenic to ferrets and mice, and can also be transmitted via the respiratory system of ferrets. According to the authors, "based on these observations, it is important to take all measures to control HPAI H5N1 virus in dairy cows to prevent further human infections."

The research was conducted by scientists at the University of Wisconsin-Madison, with collaboration from the University of Shizuoka and the University of Tokyo and the Center for Global Viral Diseases (Japan). The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), funded much of the work through its Centers of Excellence for Influenza Research and Response program.

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C Gu The et allIn animal models, a human isolate of bovine H5N1 virus is lethal and transmissible. Nature DOI: 10.1038/s41586-024-08254-7 (2024).

In Eisfeld The et all. The pathogenicity of the H5N1 bovine influenza virus and its transmissibility to mice and ferrets. Nature DOI: 10.1038/s41586-024-07766-6 (2024).

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Lauren Byrd Leotis, Ph.D., is the chief of the Viral Respiratory Diseases Section in the Division of Microbiology and Infectious Diseases at NIAID. She can be contacted to discuss the findings.

NIAID supports and conducts research at NIH, in the United States and around the world, to study and develop new methods for diagnosing, preventing, and treating infectious and immune-mediated diseases. On the NIAID website, you will find press releases, fact sheets, and other NIAID materials. NIAID website.

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