Bird flu detected in pigs – here’s why virologists are concerned

H5N1 influenza has now been detected in pigs. This was something virologists had been worrying about ever since this highly pathogenic strain of bird flu started its rapid global spread in 2020. But why were we worrying specifically about pigs? And does this case – detected on a farm in Oregon on October 29 – change anything?

It might seem odd that we care about it at all. In many ways, the initial reports of this case are – against the backdrop of a continuing viral outbreak that has devastated seabird colonies around the world, caused huge die-offs of sea lions and led to the emergence of an entirely new disease of US dairy cattle – pretty innocuous.

What we currently know is this: H5N1 bird flu infected poultry on a small American non-commercial farm, something which is sadly now quite common. In this case, there were other animals on the farm, including five pigs. Although the pigs appeared to be healthy, a nasal swab from one of them was found to contain H5N1.

We don’t yet know if the pig was actually infected or if it had just snuffled up some contaminated material from the birds. At the moment, this particular outbreak doesn’t seem to have spread into any other pigs.

And “spillover” infections on farms, where a virus from one species turns up in another, are nothing new. Back in May, H5N1 turned up in farmed alpacas in a somewhat similar incident.

To understand why pigs get virologist’s attention, we need to think about what it means for a virus to jump from one host species to another. A moment’s reflection tells us that changing host species must be an incredibly difficult thing for a virus to do.

The world is teeming with viruses that infect every species around us. If it wasn’t very nearly impossible for a virus to jump from one species into another, we’d be dealing with a new pandemic every ten minutes.

Much more subtle

The reason it’s so difficult for a virus to jump between different types of host is because viruses are fundamentally different from bacteria, or parasites: pathogens that basically just want to eat us. Viruses are much more subtle.

Viruses work by taking control of our cells and carefully reprogramming them into machines for making more viruses. Because of this, a virus infecting a new host species is like someone trying to win an argument by shouting at people in a language that they can’t understand. And this is where pigs come in.

Influenza viruses (specifically influenza A viruses, the group to which H5N1 belongs) are unusually good at crossing between different host species. They still only manage to create a new human disease once every few decades, but that’s a better hit rate than any other virus.

If we look back, most of the pandemics we know of have been caused by influenza viruses, and the threat of a new pandemic is the biggest worry we have about H5N1 now.

One of the main reasons that influenza is good at learning the language of a new host species is that, if two influenza viruses can get into the same cell at the same time, they will assemble new viruses that take some of their genes from one parent virus and some from the other. The novel virus that this creates can suddenly shift to being better evolved to its host.

For example, it could still look like an avian virus, which we have no immunity to, while having swapped most of its genes for versions that are very good at winning arguments with human cells. This is a powerful way for a virus to leapfrog towards causing a pandemic. However, it only works if a bird virus and a human virus can get into the same cell at the same time, and this turns out to be really difficult for influenza viruses to do.

It’s difficult because influenza viruses get into cells by grabbing on to a particular type of sugar molecule that coats the cell surface. This molecule can be chemically assembled in several different shapes, and while one shape of molecule is used on cells in birds (and, we now think, in cow’s udders), a different shape is used on cells in the human airway.

Mixing vessels

Bird flu viruses and human flu viruses are trying to get into cells by rattling the handles of different doors, which limits their ability to meet in the same cell. And this is where pigs come in, because it turns out that the cells in pig airways use both types of sugar molecule on their surface. Pig cells can be infected by both bird flu and human flu, making pigs a potential “mixing vessel” in which influenza viruses with pandemic potential could be brewed.

Has this happened yet? Thankfully, no. At the moment, this detection of H5N1 in a pig appears to have been an isolated incident. We don’t know how likely it is to happen again.

Indeed, there is an idea that it could be quite hard for this particular virus to infect pigs, a hypothesis supported by some experimental work and by the observation that, despite H5N1 running rampant and turning up in all sorts of animals over the last four years, this is the first time an H5N1 infection of pigs has been suspected.

Even if H5N1 did succeed in establishing sustained transmission in pigs – as it has already done in cows – what that would mean is far from certain. We know that influenza viruses can mix with each other in pigs, but we also know that the strain of influenza virus that entered pigs in 1918 then circulated in them for over 90 years before combining with other viruses to cause the 2009 swine flu pandemic.

So why did a report of H5N1 in pigs get so much attention from virologists? H5N1 has the potential to be an extremely dangerous virus for many different animals, and combining its genes with a human virus could make it much more dangerous to us.

The risks of that happening have already begun to increase as this year’s winter flu season starts for humans while H5N1 is circulating on farms in the US. Any suggestion of the virus turning up in animals that could help it to mix and match with a human influenza is a troubling reminder that H5N1 has the potential to change its capabilities very quickly.

When it comes to which animals to watch for signs of such a change happening, some animals are more equal than others. For as long as H5N1 is around, virologists are going to watch any infections of pigs with interest.

Ed Hutchinson is affiliated with the European Scientific Working group on Influenza and other respiratory viruses (ESWI) and has an unpaid position on the advisory board of PinPoint Medical. His reserach receives funding from UKRI and the Wellcome Trust.