Data highlights the need to control the cow outbreak to stop the spread of bird flu

a A new study examining the distribution of receptors to which flu viruses can attach in different tissues of cows may help explain the pattern of illness seen in the H5N1 avian flu outbreak in U.S. dairy cattle – and is also sparking debate about the implications of the outbreak cows for human diseases.

The study, a preprint which has not yet been peer-reviewed by a scientific journal, has shown that tissue from the mammary gland contains abundant receptors of the kind that bird flu viruses such as H5N1 can attach to. But tissues in the brain and respiratory tract contain much less of this type of receptor.

That fits the description of how this virus behaves in cows, with clear signs of infection in the udders, but little evidence of respiratory infections and no reports so far of cows showing neurological symptoms. This virus has been observed to affect the brains of a number of other mammalian species it can infect, including cats. Therefore, it is important to consider whether the brains of cows are also susceptible.

The work was done by scientists from the University of Copenhagen, Denmark’s Statens Serum Institut and St. Jude Children’s Research Hospital in Memphis, Tennessee.

The spread of the types of receptors – to which some bird flu viruses can attach, to others to which human flu viruses attach – raises concerns that cows could potentially give rise to a version of H5N1 or another new flu virus that can efficiently transmit to other types of receptors. and among people, the authors suggested.

“These results provide a mechanistic rationale for the high levels of H5N1 virus reported in infected bovine milk and demonstrate that cattle have the potential to act as a mixing vessel for emerging diseases. [influenza virus] generation,” they wrote.

Pigs, which can be infected with both avian and human flu viruses, have traditionally been seen as mixing vessels for new viruses that could pose a pandemic threat. That’s because when an animal is simultaneously infected with different flu viruses, the pathogens can exchange genes, a process called reassortment. That phenomenon could give rise to new virus strains with enough human genes to easily infect humans, but also enough bird flu genes that are so foreign to the human immune system that they could pose a serious risk to human health.

Cows have not been thought to pose such a risk. Although it is known that they can be infected with influenza viruses, influenza is not yet considered a major problem for cows. And until this outbreak, cows haven’t played a role in the H5N1 story.

This virus, first observed in China in 1996, is primarily a virus that infects wild birds and domestic poultry, although it has been shown to infect numerous mammal species in the nearly three decades that followed. Nearly 900 human infections have been identified in that time. About half of those people have died.

The current outbreak in the US has identified one human case: a Texas dairy farm worker whose only symptom was conjunctivitis. It is widely believed that there may have been other cases, but farmers in many cases were unwilling to cooperate with health authorities trying to investigate the outbreak, and many of the workers were also reluctant to cooperate.

Some scientists not involved in the study described the paper as interesting, but wondered whether these findings could be used to conclude that cows pose a risk to mixed vessels.

Malik Peiris, chairman of the department of virology at the University of Hong Kong’s School of Public Health, told STAT in an email that previous research has shown that cows are not very susceptible to human flu viruses. Furthermore, it would be difficult to understand how a human flu virus could reach a cow’s udder, which contains receptors for both avian and human flu viruses. “Therefore, I do not think the risk of human influenza H5N1 virus reassortment in cows is likely.”

Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan, in Saskatoon, Canada, agreed, noting that knowing which tissues a flu virus can attach to tells only part of the story. There are other factors, she said, that determine whether or not a virus can replicate in the cells it attaches to, causing an infection.

That said, Rasmussen, who researches animal diseases that can transmit to humans, is still concerned about H5N1 in cows. H5N1 infections have been confirmed so far 36 herds in nine states.

“I’m more concerned about the evolution of cow H5 toward human-to-human transmission by jumping between different hosts (bird to cow to human, cow to bird to cat, cow to cat) and from cow to cow . This selects viruses that can infect, replicate efficiently, and spread enough to spread in many different hosts, and increases the likelihood that this can happen in a human host as well,” she wrote in an email.

“These data confirm to me that it is essential to control the cow outbreak as there are many possibilities for a more transmissible human virus to emerge from it.”

The Danish researchers took samples of stored tissues – brain, respiratory tract and mammary glands – from a small number of cows and a calf. Some cows were dairy cows; others were beef cattle. They stained the tissue to see which receptors they had, whether they were for human or avian flu viruses, and for the latter whether they were the type best suited for viruses circulating among chickens or those circulating among wild ducks. A virus spillover from wild birds is believed to have caused this outbreak in cows.

They found few receptors in the brain tissue they examined. “What we found was that the flu receptors were expressed in the neurons, but at a very low level. So we also speculate that this could be the reason why no neurological symptoms have been found” among infected cattle, said first author Charlotte Kristensen. Kristensen will defend her dissertation this week and begin postdoctoral research at the university in the department of veterinary medicine and animal sciences.

One surprising finding was a lack of receptors in the ducts of the mammary glands, which the authors say argues against the idea that cows become infected through what they call an “ascending infection.” The main hypothesis for the spread of this infection among cows is that when an infected cow enters a herd, small amounts of the H5N1-contaminated milk may remain on the milking equipment and come into contact with the teats of uninfected cows, which then become infected.

While Peiris agreed that the receptor pattern in the breast ducts was surprising, he said he still believes this route of infection is the most likely. He noted that there are reports that some cows experience infection in only some – and not all – parts of their udders. “There is no other way to explain how one segment of the mammary gland becomes infected, while other segments remain unaffected,” Peiris said.

Rasmussen agreed. “These results are interesting and good to know. But I don’t think they are enough evidence to rule out contaminated milking equipment or any other hypothetical route of transmission. Especially respiratory,” she wrote.