https://www.smh.com.au/national/bird-flu-is-spreading-among-mammals-how-worried-should-we-be-20230207-p5cig3.html

-Influenza viruses bind to certain sialic acid-containing receptors on the surface of cells, using them to get inside and take over. These receptors come in multiple varieties; human influenza viruses bind to alpha-2,6 receptors, while the viruses that infect birds prefer alpha-2,3.

This difference is important. Humans also have alpha-2,3 receptors, but they tend to be deep in the lung rather than in our upper airways. That makes it very hard for H5N1 to get a purchase, giving us good protection from the virus. The tradeoff is when it does take hold, that infection is deep in our body, often leading to severe disease. This explains why bird flu infections in humans are extremely rare but often lethal: the World Health Organisation has tracked 868 cases and 457 deaths since 2003.

...Indeed, the virus isolated from the mink in Spain had an uncommon mutation that allows it to more-easily infect mammal cells.

And it does not need to take many more steps before it is a danger to humans. Lab evidence suggests as few as five specific amino acid changes are all H5N1 needs to spread effectively in humans. Wild viruses with two of these mutations have been spotted. “It’s not really a big stretch for it to happen,” says Horwood.

Is this an imminent pandemic threat? “No,” says Professor Ricardo Soares Magalhães, director of the Queensland Alliance for One Health Sciences at the University of Queensland, “the situation is indeed concerning, but not a matter for alarm.”

The Spanish researchers tested all the people who worked with the mink but did not turn up any evidence of H5N1, suggesting the virus has not picked up a mutation that enables easy spread to humans.

And CSIRO bird flu expert Dr Frank Wong points out there’s no evidence the virus has a new mutation that allows it to spread easily in mammals. The mink, which are jammed together in small cages, may be a special case. “The risk of onward, mammal-to-mammal transmission has not really changed,” he says. “It’s still a bird-adapted virus.”

Nor is the situation analogous to COVID-19. That virus was (unfortunately) unexpected by health authorities; scientists have tracked H5N1 for years and have prepared vaccines and antivirals.-

Oh, this is a good one!

What you're talking about here is tropism - what host a virus can infect, and not pathogenicity - whether or not it can make you sick and to what degree. They are related because the virus needs to be able to infect you in order to make you sick, but tropism is just one part of a much bigger picture.

Flu is even crazier than just sea lions, birds and humans. Check out this picture: https://www.semanticscholar.org/paper/Sialobiology-of-influenza%3A-molecular-mechanism-of-Suzuki/4bdb9bbce24fcc2dba5a37a65f5e33052119e4be/figure/0

Influenza can infect people, birds, pigs, cows...even whales!

Notice next to each one it has an indication of H or N with a number? That's the type of hemagglutinin (H) or neuraminidase (N) - two proteins on the surface of the fly virus that are important to the virus getting into a target cell. Notice the duck in the middle says H1-15 and N1-9? Yeah, waterfowl are the native hosts for influenza and carry all the different types in all the combinations. All the other animals are more limited. We name a virus by what H and what N it has and that's how we get H1N1, or H5N1. Hemagglutinin is really important to how the virus attaches to and enters a cell in your body. Despite it being the same protein in all different flu viruses, each number is slightly different. Each of these Hs binds to a modification on protein in your lungs called sialic acid. And... different types of animals have different sialic acids in different places in their lungs. So, for an animal to even get infected with a version of the flu it's sialic acid needs to match the virus's H.

H5 is one of the ones that scares us because it CAN infect humans, and when it does it's less than great. However, it seems like it's only possible to get an H5 virus directly from a bird and not from another human. (This is what public health people will monitor for - human to human transmission). The reason for this is where the right sialic acid for H5 is in our lungs... it's WAAAY down the bottom and you have to breathe in a lot of virus to get it there and start the infection, so it's not easy to transmit and probably doesn't spread to the rest of the lung where it could make enough of itself to infect your neighbors.

Vincent Racaniello has a good simple writeup on this: https://www.virology.ws/2009/05/05/influenza-virus-attachment-to-cells-role-of-different-sialic-acids/

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BONUS edit - there are actually more viruses than you might expect with a broad host range. Poxviruses can get around, you can share SARS-CoV-2 (COVID) with your dog and the deer in your yard, and arboviruses HAVE TO infect both insects and humans to be passed along successfully.

"Zoonotic" is generally a term for a disease readily transmissible to humans or a disease that has a very similar human counterpart, and often that does not transmit readily from person to person -- though obviously there are a lot of exceptions, my definition is only a generalization.

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That said H5N1 does seem to be general enough that it can infect a wide variety of warm-blooded organisms, and to spread between many (though not all) of those species without birds - and that is very disturbing, because we know only one of two critical facts about H5N1 in people:

• We know we can get it, a number of people in close contact with birds have come down with it. I'm talking people who clean coops (read: barns) in chicken farms and that kind of thing, not a person with a bird feeder on their balcony.
• We don't know what keeps it from spreading from person to person. It can get you sick enough to need a hospital, if not kill you, but for whatever reason an ill person is not (yet) contagious to other humans. But it can spread in other mammals, eg. from one mink to another. Are we just not dense enough (population wise), the mink farm was loads of them all in an enclosure in constant close contact. Or a time factor, like it takes hours to acquire the load needed to trigger an infection, and the few minutes of contact human to human is not enough? Or is it biological, eg. it can't hijack the reproduction mechanics necessary to reach the level where it would be contagious? Or something else? We don't know, and considering how severe of a disease this is that is very troubling.

edit: to be clear, there are some solid information/fact-based hypotheses that posit why it may not be human-human transmissable (see the rest of this thread), but we don't know which one or perhaps some/all the possible reasons are the 'correct' ones; this is ELI5 not ELIdoctor

As others have said, no it is not particularly unique in terms of the amount of species hosts it affects.

Animal cells come in different shapes and sizes but other than that, they are they are functionally and anatomically the exact same across different species. It does not matter much that we humans are closely related to other primates and not closely to birds, sea lions, etc. because we have the same cells either way.

The relevant part in terms of whether the virus can attach or not is due to things like different animo acid / receptors / acids covering the animal cell and preventing the virus from binding, host body temperature, the virus not producing enough of a particular protein to duplicate given the size/ immune system of their host, etc.

For example, rabies does not typically live in squirrels because their blood is not warm enough for the virus to be comfortable (~95 degrees F), but it does in raccoons (101-106 degrees F). The difference is not that significant but is enough to affect who the virus typically host.

Also,

>I know diseases like HIV are thought to come from primates, which makes sense: we're so closely related

Humans are primates :)

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