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/BraveOthello → u/SquirrellyBusiness]

IIRC all of the mammalian prion diseases are built of variations of the same highly conserved protein, it's the reason humans can contract vCJD from a cow infected with BSE in the first place.

[u/dr_jigsaw → u/BraveOthello]

It’s the same protein in CWD, but as another poster said Prnp has a strong species barrier. CWD has never been documented to cross between cervids and humans, but if you are a hunter you should have the head tested and avoid CWD-infected meat just in case.

[u/apic0mplexa → u/dr_jigsaw]

What I don't understand is how the species barrier can be stronger when it's the same protein. I just can't solve that knot in my brain

[u/Liquid_Hate_Train → u/apic0mplexa]

It’s the same protein, but not the exact same misfolding of that protein. Some animals will recognise certain misfoldings for destruction and others not.

[u/Lt_Duckweed → u/apic0mplexa]

It isn't the exact same protein, the amino acid sequence varies a bit from species to species (though less than many other proteins) and some sequences are more/less vulnerable to a specific misfold.

[u/PumpkinBrain → u/dr_jigsaw]

Given what has been said about prions not evolving, does that mean humans are safe from CWD? IE if it were going to infect a human it would have already?

[u/RetardedWabbit → u/BraveOthello]

IIRC all of the mammalian prion diseases are built of variations of the same highly conserved protein...

And that protein is...Major prion protein(PrP)? Well, that's easy to remember at least but terrible abbreviation. Seems to have complicated functions regulating long term nervous system development. (Also technically not all known prion diseases are from this)

All of the prions look extremely similar too, forming naturally super stable and resistant shapes. They go from helixes, which biology is usually pretty good at interfacting with, to "tight" sheets that it's not.