> Maybe you're just saying that a prion isn't as good at replicating as a virus? It seems like a difference of degree rather than kind.

They are qualitatively different.

A virus infects a cell, and critically, can quickly adapt (through random mutations) in an unthinking war between the various forces of the immune system and transmission mode efficacy; A prion does not evolve, it's a misfold of a single type of protein. If you want to compare it to a virus, it's like a virus that is incapable of replicating anything other than an exact copy - and can also only replicate itself using a particular cell (one type of protein).

Why the human body cannot effectively defend itself against particular propagating misfolded proteins is a mystery to me though... perhaps it's too low level to be identified by the immune system as something to attack, much like a poison.

A protein can misfold in countless ways, and there are countless of proteins to misfold.

That a virus can be a big and complicated structure does not mean that smaller and simpler structure is fundamentally different.

Viruses themselves also have many different modes of operation, with things like virophages, satellite virus and giant virus showing just how unclear the term "virus" is.

> A protein can misfold in countless ways, and there are countless of proteins to misfold.

They are countable, but yes there are many ways, but that alone doesn't mean it's capable of meaningfully evolving. It's a search space multiple orders of magnitude smaller than a piece of DNA, so it's easy to see how a different successfully propagating misfold will be significantly less likely when starting from an existing propagating misfold.

If you are suggesting one propagating misfolded protein can, by chance, misfold into another propagating misfolded protein at a rate fast enough to become adaptive... then it's qualitatively the same as a virus, but I don't see this as likely given the significantly smaller search space.

The largest protein we produce is about 27k amino acids, more complicated than most virophages. That is merely the biggest we produce. I know of no upper limit on protein complexity, and that is before even taking folding options into consideration.

The space of possible proteins - and thus prions - is not at all limited, neither figuratively nor literally. It is most certainly not "countable" without some Nobel-prize inducing discovery.

> The largest protein we produce is about 27k amino acids, more complicated than most virophages

The only known human prion proteins seem to be a few orders of magnitude smaller than that though, and they don't appear to adapt.

Are you saying it's possible for prions to emerge from large proteins with the ability to adapt?

They may be suggesting that prions don't have a large space to evolve within through random mutation