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The example in the article has very little transmissive ability because it grows in the brain and eyes. If there were a respiratory prion disease that could be

The example in the article has very little transmissive ability because it grows in the brain and eyes. If there were a respiratory prion disease that could be much different. By nature of being a protein they are simpler and harder to eliminate than bacteria or viruses: > In a particularly vexing twist, prions are also nearly impervious to destruction, even when attacked using a strenuous combination of disinfectants, heat, and pressure.

dahfizz 8y ago
> If there were a respiratory prion disease that could be much different. Not really. The point your parent is making is that prions themselves don't reproduce like viruses and bacteria. Its basically impossible for a large scale breakout to occur and spread.
- DennisP 8y ago
  But they do reproduce, by causing other proteins to misfold. If they didn't reproduce at all, then ingesting a few prions wouldn't cause any problems. They can't reproduce outside of the body, but neither can viruses.
  - jamiek88 8y ago
    Yes but they can only warp their own specific kind of protein not take over an entire reproductive ability of the native cell. It’s orders of magnitude less reproduction.
- ergothus 8y ago
  Can you explain why? I'm not saying this is wrong, but they definitely replicate (by encountering and warping other proteins), so are you (and grandparent) saying that the replication rate is too slow? If so, why? Are you saying we have no means of transmitting proteins? (that sounds wrong, though I've been wrong before) From my (ignorant, despite being interested in prions for decades now) perspective, you have something that (1) can replicate, (2) is durable (3) is harmful, and only the relative rarity of prions in general (because 1 and 3 are physically unusual to combine) have kept them from being a general problem. As we tinker with DNA and thus look into creating new proteins and factors that would influence protein-folding, I'd think it's worth taking the matter seriously (though not fear-mongering), certainly as part of our need to understand proteins better anyway. What are my faulty assumptions?
  - PeterisP 8y ago
    A prion can't arbitrary replicate from "food" or "host", its replication is more like a damaged version of protein X that can damage that same protein X if it encounters it. In many aspects it stays the same protein - the exact same DNA, the exact same sequence, just folded differently. A virus can overtake a cell and mobilize its resources to create a bajillion copies of that virus. A prion can transform only as much copies of that protein as that cell has made in its normal processes.
    - ergothus 8y ago
      A bacteria replicates at a much smaller rate than a virus. A virus requires a cell to replicate, bacteria require a much more limited range of hospitable environments. Both bacteria and viruses "attempt" to create exact copies, just as a prion does. Admittedly prion replication probably has more accuracy, but that prions occur at all indicates the process allows for natural selection. These don't seem to put prions outside of the "replication" category - they replicate by encountering other proteins, so they are in a body. Their rate of replication is limited (or boosted) by the rate of encountering these proteins. They attempt to create copies of themselves with the chance of failure or different end result.
- deleted 8y ago
  [deleted]
nonbel 8y ago
How is this at all a "twist"? The reason you cannot deactivate prions using these methods is that they are meant to denature protein. Prions are "amyloids"/beta-sheets, which means they are already in the lowest-energy state. This lowest-energy-state is exactly why the presence of prion can serve as a nucleation point for other proteins to denature into beta-sheets.
- travisoneill1 8y ago
  I don't care whether or not it's a "twist". I care that there is an entire class of pathogen that we don't know how to sterilize a surface of.
  - nonbel 8y ago
    You just use bleach and then autoclave: >"combining autoclaving (even at 121 degrees C) with a sodium hydroxide treatment is extremely effective." https://www.ncbi.nlm.nih.gov/pubmed/10658760 https://www.ncbi.nlm.nih.gov/pubmed/10658760
    - coryrc 8y ago
      Bleach is sodium hypochlorite; sodium hydroxide is lye/caustic soda.
      - nonbel 8y ago
        Yea, sorry. Earlier in the abstract it mentioned sodium hypochlorite then I didnt read closely: "Strong sodium hypochiorite solutions achieve inactivation but other chlorine-releasing compounds are less effective" Usually there is some sodium hydroxide in standard sodium hypochlorite bleach solution as well though, perhaps that explains why they reported it is the most effective of the chlorine bleaches.
  - arkades 8y ago
    It’s been said a few times in this thread that that is a misrepresentation by the article. Allow me to quote at length from an article on the topic by Brown and Lee: One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denature, or modify proteins do have activity against prions [7]. The PrP purified from the brains of scrapie-infected animals (PrPSc) can be inactivated by prolonged autoclaving (at 121ºC and 15 psi for 4.5 hours), or immersion in 1N NaOH (for 30 minutes, repeat three times), or immersion in concentrated (>3 M) solutions of guanidine thiocyanate [10]. However, certain cautions prevail; it appears that inadequate autoclaving can establish heat-resistant subpopulations that fail to diminish with a further cycle of autoclaving [11]. Stainless steel instruments also may retain infectivity even after treatment with 10 percent formaldehyde [12,13]. Newer decontamination techniques are being investigated. There has been some success in sterilization using a combination of sodium dodecyl sulfate (SDS), proteinase K, and pronase [14]. A radio-frequency gas-plasma treatment has been shown to effectively decontaminate surgical instruments [15]. Another group has tested a decontamination formula combining copper metal ions with hydrogen peroxide [16].
kurthr 8y ago
If any of the proteins involved in respiration were susceptible to lower free energy confirmations (different foldings that were entropically favorable in vivo) then they likely would already be present, there would be such a prion and life that used those proteins would be highly selected against. Respiration is very common in animals. As it is, very few proteins in humans have alternate favorable form (by luck or selection?). The exception appears to be the extremely complex and relatively new nervous system of mammals. I'd guess that our immune systems might be another place to look, but that is very highly tested. Frankly, this seems like a susceptibility that is rare because it is chemically odd not that there is a lack of potential exploitation. Luckily, the range of creatures that share our respiration system far exceeds the range of creatures which share our recently evolved nervous system.

dahfizz 8y ago

> If there were a respiratory prion disease that could be much different. Not really. The point your parent is making is that prions themselves don't reproduce like viruses and bacteria. Its basically impossible for a large scale breakout to occur and spread.

DennisP 8y ago
But they do reproduce, by causing other proteins to misfold. If they didn't reproduce at all, then ingesting a few prions wouldn't cause any problems. They can't reproduce outside of the body, but neither can viruses.
- jamiek88 8y ago
  Yes but they can only warp their own specific kind of protein not take over an entire reproductive ability of the native cell. It’s orders of magnitude less reproduction.
ergothus 8y ago
Can you explain why? I'm not saying this is wrong, but they definitely replicate (by encountering and warping other proteins), so are you (and grandparent) saying that the replication rate is too slow? If so, why? Are you saying we have no means of transmitting proteins? (that sounds wrong, though I've been wrong before) From my (ignorant, despite being interested in prions for decades now) perspective, you have something that (1) can replicate, (2) is durable (3) is harmful, and only the relative rarity of prions in general (because 1 and 3 are physically unusual to combine) have kept them from being a general problem. As we tinker with DNA and thus look into creating new proteins and factors that would influence protein-folding, I'd think it's worth taking the matter seriously (though not fear-mongering), certainly as part of our need to understand proteins better anyway. What are my faulty assumptions?
- PeterisP 8y ago
  A prion can't arbitrary replicate from "food" or "host", its replication is more like a damaged version of protein X that can damage that same protein X if it encounters it. In many aspects it stays the same protein - the exact same DNA, the exact same sequence, just folded differently. A virus can overtake a cell and mobilize its resources to create a bajillion copies of that virus. A prion can transform only as much copies of that protein as that cell has made in its normal processes.
  - ergothus 8y ago
    A bacteria replicates at a much smaller rate than a virus. A virus requires a cell to replicate, bacteria require a much more limited range of hospitable environments. Both bacteria and viruses "attempt" to create exact copies, just as a prion does. Admittedly prion replication probably has more accuracy, but that prions occur at all indicates the process allows for natural selection. These don't seem to put prions outside of the "replication" category - they replicate by encountering other proteins, so they are in a body. Their rate of replication is limited (or boosted) by the rate of encountering these proteins. They attempt to create copies of themselves with the chance of failure or different end result.
deleted 8y ago
[deleted]

nonbel 8y ago

How is this at all a "twist"? The reason you cannot deactivate prions using these methods is that they are meant to denature protein. Prions are "amyloids"/beta-sheets, which means they are already in the lowest-energy state. This lowest-energy-state is exactly why the presence of prion can serve as a nucleation point for other proteins to denature into beta-sheets.

travisoneill1 8y ago
I don't care whether or not it's a "twist". I care that there is an entire class of pathogen that we don't know how to sterilize a surface of.
- nonbel 8y ago
  You just use bleach and then autoclave: >"combining autoclaving (even at 121 degrees C) with a sodium hydroxide treatment is extremely effective." https://www.ncbi.nlm.nih.gov/pubmed/10658760 https://www.ncbi.nlm.nih.gov/pubmed/10658760
  - coryrc 8y ago
    Bleach is sodium hypochlorite; sodium hydroxide is lye/caustic soda.
    - nonbel 8y ago
      Yea, sorry. Earlier in the abstract it mentioned sodium hypochlorite then I didnt read closely: "Strong sodium hypochiorite solutions achieve inactivation but other chlorine-releasing compounds are less effective" Usually there is some sodium hydroxide in standard sodium hypochlorite bleach solution as well though, perhaps that explains why they reported it is the most effective of the chlorine bleaches.
- arkades 8y ago
  It’s been said a few times in this thread that that is a misrepresentation by the article. Allow me to quote at length from an article on the topic by Brown and Lee: One of the characteristic features of prions is their resistance to a number of normal decontaminating procedures. These pathogens are resistant to processes affecting nucleic acids, such as hydrolysis or shearing [9]. However, agents that digest, denature, or modify proteins do have activity against prions [7]. The PrP purified from the brains of scrapie-infected animals (PrPSc) can be inactivated by prolonged autoclaving (at 121ºC and 15 psi for 4.5 hours), or immersion in 1N NaOH (for 30 minutes, repeat three times), or immersion in concentrated (>3 M) solutions of guanidine thiocyanate [10]. However, certain cautions prevail; it appears that inadequate autoclaving can establish heat-resistant subpopulations that fail to diminish with a further cycle of autoclaving [11]. Stainless steel instruments also may retain infectivity even after treatment with 10 percent formaldehyde [12,13]. Newer decontamination techniques are being investigated. There has been some success in sterilization using a combination of sodium dodecyl sulfate (SDS), proteinase K, and pronase [14]. A radio-frequency gas-plasma treatment has been shown to effectively decontaminate surgical instruments [15]. Another group has tested a decontamination formula combining copper metal ions with hydrogen peroxide [16].

kurthr 8y ago

If any of the proteins involved in respiration were susceptible to lower free energy confirmations (different foldings that were entropically favorable in vivo) then they likely would already be present, there would be such a prion and life that used those proteins would be highly selected against. Respiration is very common in animals. As it is, very few proteins in humans have alternate favorable form (by luck or selection?). The exception appears to be the extremely complex and relatively new nervous system of mammals. I'd guess that our immune systems might be another place to look, but that is very highly tested. Frankly, this seems like a susceptibility that is rare because it is chemically odd not that there is a lack of potential exploitation. Luckily, the range of creatures that share our respiration system far exceeds the range of creatures which share our recently evolved nervous system.