A highly pathogenic avian influenza (HPAI) H5N1 virus isolated from the eyes of a farm worker infected through contact with dairy cows was transmitted to mice and mice infected in a high-containment laboratory environment, according to a new study published in the journal Nature. It has been shown to be lethal in ferrets. Researchers also found that a virus isolated from a worker who experienced mild inflammation of the cornea (conjunctivitis) can be transmitted through the air between separated ferrets and binds to cells in human respiratory tracts. They also discovered that it may be possible to reproduce them.
The virus isolated from this worker is called huTX37-H5N1 and has a mutation (PB2-E627K) that is frequently seen in avian influenza viruses, which typically makes the virus more efficient at replicating in mammals. It will be. These mutations highlight the need for continued surveillance and evaluation of the virus due to the current H5N1 outbreak.
The study also showed that the bovine H5N1 virus is sensitive to the polymerase inhibitor class antivirals favipiravir and baloxavir marboxil (trade name Xofluza), as well as the neuraminidase inhibitor zanamivir. This virus is less susceptible to oseltamivir (Tamiflu), another neuraminidase inhibitor.
In laboratory experiments, huTX37-H5N1 was replicated in human corneal cells and lung cells. The researchers found that the lethal dose of huTX37-H5N1 in mice is less than 1 plaque forming unit (PFU), while the lethal dose of bovine H5N1 virus isolated from the milk of lactating cows is 31.6 PFU. It was decided. The huTX37-H5N1 virus also infected each of the 15 different mouse tissues tested, with the highest virus levels detected in respiratory tissues.
The researchers also infected ferrets with high doses of huTX37-H5N1. Influenza infection in ferrets is more similar to influenza infection in humans than influenza infection in mice. All infected ferrets died within five days, and scientists found high levels of the huTX37-H5N1 virus in their respiratory systems in all tissues taken. In a previous study, researchers infected ferrets with the bovine H5N1 virus, which caused severe disease but limited lethality.
To assess respiratory infections, scientists placed healthy ferrets in cages approximately 5 centimeters away from ferrets infected with one of four decreasing doses of huTX37-H5N1 a day earlier. . All directly infected ferrets died within six days, and depending on the exposure dose, 17 to 33 percent of nearby animals were infected by droplet transmission. These results indicate that bovine HPAI H5 viruses isolated from infected individuals can be transmitted to mammals via respiratory droplets, although with limited efficiency.
The authors note that people infected with the huTX37-H5N1 virus did not develop severe symptoms. In fact, most human cases reported in this outbreak experience conjunctivitis and mild respiratory symptoms. Researchers speculate that ocular infection with low doses of bovine H5N1 virus may cause localized conjunctivitis without serious disease in humans. They say multiple exposures to seasonal human influenza viruses may provide low levels of protection against the currently circulating HPAI H5N1 virus, but additional research is needed.
In summary, this study characterizes the huTX37-H5N1 isolate, showing that it has the potential to replicate within cells of the human respiratory tract, is pathogenic in mice and ferrets, and has the potential to be transmitted by the respiratory route. I discovered that there is. With ferrets. The authors state, “Based on these observations, every effort should be made to prevent the occurrence of HPAI H5N1 in dairy cows to limit the potential for further human infection.” .
Scientists from the University of Wisconsin-Madison led the study, along with collaborators from Shizuoka University, the University of Tokyo, and Japan’s Global Center for Research on Infectious Diseases. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, funded much of the research through its Influenza Research and Response Centers of Excellence Program.
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NIH/National Institute of Allergy and Infectious Diseases
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