The avian influenza virus is capable of infecting cattle, making them a potential source of infection for humans. A researcher says that understanding these connections is important because dairy cows can transmit infection to other animals and humans.
At the end of March, virologists all over the world became alerted after an outbreak of the highly pathogenic avian influenza virus (H5N1) was first detected in cows in the United States and has since spread to more than 90 herds in 12 states.
Three people who work with cows were infected with the virus during this period, and H5N1 is at the top of the list of viruses feared to cause a new pandemic.
Further, scientists found that the milk of the dairy cows with which the people worked was full of H5N1 viruses.
This was both shocking and surprising because it has long been generally acknowledged that the avian influenza virus cannot infect cattle. However, a new study shows how this can happen anyway.
“Since 2020, we have developed a tool to identify and characterise virus-relevant receptors on the surface of cells, and this method enabled us to discover that the receptors H5N1 needs to penetrate cells are also expressed in bovine mammary glands,” explains a researcher behind the study, Lars Erik Larsen, Professor, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
The research, which is under revision for peer-reviewed publication, has been published as a preprint in bioRxiv. The researchers chose this publication method because they wanted to communicate their results rapidly.
Receptors not specifically developed to benefit viruses
The method the researchers developed identifies the receptors that viruses need to penetrate cells more easily and rapidly.
For example, H5N1 must use a specific type of receptor that is present in the airways of birds and deep in people’s lungs and in their eyes.
SARS-CoV-2 uses other type of receptors that are present in both humans and some other mammals, including mink.
The receptors did not specifically evolve to enable cells to become infected with H5N1 or SARS-CoV-2 and serve a different purpose in the tissue, but viruses have figured out how to use the natural transport pathways to find their way into the cells.
“We know that H5N1 does not easily infect the respiratory tract of cows, and therefore we never thought that cows could be infected with it. We were therefore surprised that this could happen anyway and that the cows could also infect people,” says Lars Erik Larsen.
Influenza receptors abundant in the udders
The researchers looked for the relevant receptors in cows’ mammary tissue and found that this tissue is filled with exactly the receptors that H5N1 needs to enter the cells. Influenza viruses being able to infect cows therefore makes sense.
According to Lars Erik Larsen, viruses can find their way into the udders of cows in two ways.
One possibility is that H5N1 can get into their bloodstream and thereby reach the udders, where the relevant receptors for entering the cells are present.
Viruses could also enter through the teat canal and then multiply into billions of viruses, which can infect the next cow – or an unfortunate person.
“One can imagine a scenario in which the people who contracted avian influenza from cows in the United States were infected by getting milk from infected cows in their eyes. This is possible because the receptors H5N1 needs to penetrate the cells are present in people’s eyes,” explains Lars Erik Larsen.
He elaborates that the three people infected in the United States all had eye infections before they were diagnosed with avian influenza.
Getting closer to people
The results raise several questions. For example, could the relevant receptors for H5N1 also be in the mammary glands of pigs or, for that matter, humans?
The researchers will investigate this in the future, since it is important for understanding possible transmission routes for viruses.
This may be especially relevant for pigs, since the fear is that if the avian influenza virus can infect pigs, this could create a human epidemic.
The more mammals viruses can infect, the greater the probability that they can also infect people.
For example, when a virus infects an animal, the fear is that it not only figures out how to penetrate the cells through one type of receptor but then learns to do this through several types.
This increases the likelihood that avian influenza will adapt and penetrate cells through receptors, of which people have many on the surface of lung cells.
“So far, avian influenza has been found in 35 wild mammal species, in which the virus can also penetrate the brain and blood. The fear is that the virus will soon discover how to infect people and transmit between people,” notes Lars Erik Larsen.
Pandemic concerns
The reason for the great interest in avian influenza is that it is gradually becoming more widespread, infecting chickens, pigs, cows and some people, and because H5N1 is associated with a mortality risk of 50%.
Researchers and health institutions are therefore closely monitoring what the virus can infect, how good it is at doing this and whether it will at some point figure out how to infect people.
“The nightmare scenario is an extensive pandemic with a virus that can spread easily between people with a mortality rate of 50%. This explains why nobody likes H5N1 and why we are monitoring it and trying to understand what it can infect and how it does this. The good thing about this virus, however, is that in cows, for example, it has ample opportunity to infect other cows without having to adapt to receptors that are more relevant to humans,” concludes Lars Erik Larsen.
