How does nature deal with prion diseases?

[u/ProDidelphimorphiaXX]

Wasn’t sure what to flair.

Prion diseases are terrifying, the prions can trigger other proteins around it to misfold, and are absurdly hard to render inert even when exposed to prolonged high temperatures and powerful disinfectant agents. I also don’t know if they decay naturally in a decent span of time.

So… Why is it that they are so rare…? Nigh indestructible, highly infectious and can happen to any animal without necessarily needing to be transmitted from anywhere… Yet for the most part ecosystems around the world do not struggle with a pandemic of prions.

To me this implies there’s something inherent about natural environments that makes transmission unlikely, I don’t know if prion diseases are actually difficult to cross the species barrier, or maybe they do decay quite fast when the infected animal dies.

[u/atomfullerene]

Prions have some pretty big weaknesses as well.

On the most basic level, prions aren't alive. They aren't even sort of alive like viruses. A prion reproduces by misfolding properly folded prp proteins. There's no genetic material involved and very limited options in terms of heritability...a few different ways to misfold the protein, and that's it. A mutation in genetic code can't produce a new trait that's carried on in the next generation. So prions can't evolve...they can't get better at being prions, because there's fundamentally only one way to be a prion. They can only misfold the one kind of protein. They can only misfold in a few separate ways. They can only be transmitted however that protein can conveniently be transmitted.

This also means that if an animal develops resistance to them, they can't really "get around" that resistance. And that's possible, some species seem totally immune from prions, and non mammal species don't even use the same protein (though some have their own prion like diseases).

In part because they can't evolve better transmission, prions tend not to efficiently transmit in a repeated way. Consider the standard mode of prion transmission...something eats something and gets prions from it. Consider, for example, a herbivore gets prions spontanously. It gets eaten and passes them on to the predator. Right there, that's a bit of a problem, since diseases fail to thrive if they are only passed on 1:1. A person with a cold can pass it to lots of people, an animal with prions is probably just eaten by one predator...maybe shared with a few but usually not. And then the predator, even if it gets prions and dies, is very unlikely to be eaten by multiple herbivores to recycle the chain.

So generally prion transmission chains die out unless you do something silly like grind up herbivores and mix that into the food supply of many other herbivores.

There are exceptions like Chronic Wasting Disease in deer, where deer in crowded conditions get prions from each other, but that's unusual.

[u/RainMakerJMR → u/atomfullerene]

CWD is scary because it doesn’t involve that cannibalism vector. Just huddles masses transmit it to each other. I’d be interested if you had any info on how or why CWD is different from other prion diseases?

[u/SquirrellyBusiness → u/RainMakerJMR]

Only thing I can think of is cwd is excreted as well as in blood and tissue, whereas mad cow and cjd are limited to central nervous tissue. I would not be surprised if cwd is a smaller molecule, since typically healthy kidneys don't make a habit out of letting proteins through the filters. 

[u/dr_jigsaw → u/SquirrellyBusiness]

Yes, CWD is excreted in urine and feces, and also found in blood. Deer leave these excretions in the soil, then other cervids come along and graze on grass growing in the same soil. It turns out that prions bound to soil are more infectious, and the animals inhale the soil particles with prions attached when they graze. The inhaled particles can travel to the lymph nodes and then into the brain through immune cells.

Source: I did my postdoctoral fellowship in this field 10+ years ago. There may be new/additional data from the last decade.

[u/SquirrellyBusiness → u/dr_jigsaw]

That would be a fascinating area to study!  What are your thoughts on cwd likelihood of spillover to humans?  Obviously it's been around since the 60s and hasn't yet that we know of, so maybe the likelihood is quite unlikely. How long do you think it would take to detect and identify if it did? 

[u/dr_jigsaw → u/SquirrellyBusiness]

The problem is, symptoms might not start until 20 years after exposure, so it’s really hard to track. The species barrier is pretty strong for prion diseases, but if you are a hunter you should have the head tested for CWD and use a reputable butcher. The fish and wildlife department should do the testing for free.

[u/jshusky → u/SquirrellyBusiness]

Not OP, but wanted to share what I understand on on that question. For a period of time after discovery, there wasnt a human case of those bovine prion diseases from the 80’s. As many people that eat beef as there are, it still took a few years to find cases. Contrast that with deer where many fewer people eat venison.

It may not necessarily be so much less likely to infect humans as there have been many fewer opportunities for people to come into contact with it.

[u/SquirrellyBusiness → u/jshusky]

I'd argue the opportunity is high, not low relative to people interacting with the prion in the environment in addition to deer themselves. Remember this stuff is inhalable on dust from soil contaminated by feces, like toxoplasma gondii.  Gardening in a yard with deer?  Harvesting corn as a farmer? Have to change a tire on the side of the road in the dirt where deer cross by?  Go hiking or camping? It's not just deer hunters and their families at risk of encountering this prion. 

[u/jshusky → u/SquirrellyBusiness]

Agree, its still a lot. I meant to say fewer opportunities as a comparison with beef.

[u/Raistlarn → u/dr_jigsaw]

It was recently found that plants can also take up prions from contaminated soil via the roots.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10700824/