r/science Oct 07 '22 Silver 1 Helpful 1

Study finds SARS-COV-2 encodes a protein that turns off our viral defense genes Biology

https://rdcu.be/cWXAV
14.2k Upvotes

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u/xixouma Oct 07 '22 edited Oct 07 '22 Silver Gold Helpful Wholesome Ally Outstanding Contribution

Virologist here. This is a common immune escape mechanism for viruses, they imitate cellular components to detract them from their normal function. See also this paper on influenza virus doing the same thing: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3598589/

This is something viruses use to get past very immediate defenses that all of our cells have to various levels. This is not theoretically aimed at longer term immune suppression, although more research could be done to find a link there.

Ask me anything

Edit: this really took off, glad to see some interest in the subject, it's awfully exciting. Thanks for the awards kind strangers.

I'm going to log off for a bit, need to get back to the lab for a bit, sorry everyone, I'll try to get back to this later.

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u/scootymcpuff Oct 07 '22

Ask me anything

So the headline basically reads “SARS-COV-2 virus does what pretty much every other virus does”?

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u/xixouma Oct 07 '22

Yes, if you really want a TLDR haha. What's more interesting is the specific mechanism by which it does it and the questions it raises. It mimics a host protein to distract other host processes from doing their job properly. There's a huge amount of potential follow up from this: which specific processes is it trying to divert by mimicking this protein. It seems like it targets DNA regulatory mechanisms, but it would be very interesting to know exactly which ones

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u/AphantasianArt Oct 07 '22

Does covid infection permanently damage your body's response to all viral infection, the SARS-COV-2 virus in general, or a particular strand of the covid virus? Or is it not permanent?

I know this is r/science and we anecdon't around these parts but I swear, all my life, I've been the kind of person who colds bounce off of but after my first covid infection, colds take me out like a sniper.

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u/xixouma Oct 07 '22

Not a whole lot is known about long COVID and why people become more susceptible to other viruses. But I would gamble that it isn't permanent, we are generally reasonably good at recovering from things. I hope I'm right but I can't say that I really know. It's a hot research topic

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u/TransposingJons Oct 07 '22

I, and many ME/CFS sufferers, recall having a nasty infection (mine was flu-like) prior to the onset of our conditions. My onset was 9 years ago.

Almost all of us had doctors tell us "It's in your head.", so imagine our interest when Long Covid sufferers started describing our symptoms (extreme fatigue, brain fog, and others). We're desperate for medical professionals to take us seriously. Many couldn't hold on, and took their own lives. I've been close myself.

I hope your work points towards a remedy someday. These symptoms steal your life from you.

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u/tictac_93 Oct 07 '22

I was getting really run down from CFS in college, a couple years after having a server case of mono and a couple months after a nasty sinus infection. It ended up being a gluten allergy that suddenly got activated, and it was the same (+ some other dietary things) in my dad who had been suffering since he was in grade school. If you haven't tried elimination diets yet it could be worth a shot!

I feel for you, especially not being taken seriously by doctors. Or at best, bewildering them. I was starting to wonder if this is just how everyone feels, since I was still high functioning as long as I had a lot of caffeine. Now the fatigue is mostly gone but my head is nowhere near as sharp as it used to be...

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u/bLINgUX Oct 07 '22

I don't personally deal with this sort of thing but a friend of mine had similar issues for years and then he found elimination diet and said it changed his life. He said he thought he was eating "healthy" but found that some healthy foods were causing his issues. He used this app https://play.google.com/store/apps/details?id=com.monashuniversity.fodmap and told me going through this process sucked butt it ultimately worked. He told me he has been feeling much better since and he looks much better as well versus the really tired and such that he was before. I think it's been somewhere between 6 months to a year since he started this and he's been clearly much happier since.

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u/tictac_93 Oct 07 '22

I can only speak to what my family's experienced, but I know my brother ended up being sensitive to basically all nightshades, my Dad can't tolerate garlic, onions bother me... it's a rabbit hole, and I don't always avoid the foods I know bother me but at least I know when I'm gonna get myself into trouble.

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u/jadero Oct 07 '22

As long as it's not like measles, which can trash immune memory cells, taking 2-3 years to fully recover.

https://asm.org/Articles/2019/May/Measles-and-Immune-Amnesia

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u/SamTheGeek Oct 07 '22

Worth remembering that the oldest known SARS-CoV-2 case is around three years old (the estimates of first human transmission are dated to October 2019). So we literally cannot yet know for sure whether long COVID is permanent or not.

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u/jadero Oct 07 '22

Oh, yeah, I was just expressing a general anxiety, not speculating.

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u/iupuiclubs Oct 07 '22

I had the worst "flu" I've ever received in Oct 2019.

I remember not being able to walk further than 20 feet, being constantly out of breath, and missed a doctors aptment because I couldn't get out of bed exhaustion wise.

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u/SamTheGeek Oct 07 '22

Unless you were in central China, it’s unlikely to have been Covid. It didn’t start showing up in sewer samples in the west until late January 2020 (they did go back and test earlier ones, as far as I know they haven’t found any SARS 2 in earlier, well, poops)

E: There was something else nasty going around in late 2019, not sure if it was the flu or just a bad cold. A bunch of my friends were sick too.

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u/OldDog1982 Oct 08 '22

There was a respiratory virus in my town that was sickening people as early as Nov 2019; it was not identifiable. I feel certain it was Covid from the symptoms.

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u/katarh Oct 07 '22

We know that measles does exactly that!

BBC did a pretty good layman's explanation of it a while ago.

https://www.bbc.com/future/article/20211112-the-people-with-immune-amnesia

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u/crazyrockpainter Oct 07 '22

Wow this is a fascinating article. So many of my mom friends are blaming their kids getting sick a lot on isolation/masking/“immunity debt” but I would not be surprised to see studies on covid impacting the immune system similarly to this.

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u/canucklurker Oct 07 '22

As another anecdotal response - Since I had COVID in 2020 I seem to catch every cold and flu that comes around. I can still fight them off normally once I get them.

I have been looking for further information on this but have come up empty handed

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u/rainbow_mosey Oct 07 '22

I just want to say-- I've read your responses so far on here and I really appreciate your humanity and ability to stay on topic. We should all try to be more "they're not idiots; it's just complicated" and "that's outside the purview of this paper" and "I don't have evidence for that specifically." Thanks!!!!

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u/xixouma Oct 07 '22

Happy to contribute to a healthy discussion

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u/chickenstalker Oct 07 '22

90% of science is figuring out what question to ask.

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u/LonePaladin Oct 07 '22

Douglas Adams managed to capture that really well in The Hitchhiker's Guide to the Galaxy. A supercomputer deducts that the answer to The Ultimate Question About Life, the Universe, and Everything is "42", which then prompts its operators to ask, "What's the question then?"

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u/[deleted] Oct 07 '22

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u/[deleted] Oct 07 '22

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u/[deleted] Oct 07 '22

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u/Diplomjodler Oct 07 '22

Could this discovery lead to better medications against the virus?

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u/xixouma Oct 07 '22

See previous comment, but yes this is exactly the point of this sort of research. Understand the molecular mechanisms by which the virus uses our cell to replicate can guide drug design to target these mechanisms. This is how anti HIV drugs are developed, they specifically target steps of the viral life cycle, and they are really good at it, especially used in combination

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u/gormlesser Oct 07 '22

Is this actually a noteworthy finding then or just another brick in the wall of knowledge about how this novel pathogen functions?

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u/xixouma Oct 07 '22

Hi, this is a fantastic finding. This is exactly my field of research. Viruses are little molecular machines that reverse engineer our cells to make more of themselves. Understanding how they do that is critical to come up with drug options, which there are very few of at the moment, and generally for novel pathogens

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u/NorthStarZero Oct 07 '22

Is there a metric for virus complexity?

A score for how many “lines of code” it contains, and thus, the number of possible functions it could execute?

If yes, where does COVID 19 score?

If no, is there research in this area?

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u/xixouma Oct 07 '22

Interesting question. No not really, they are all very complex or simple depending on how you view it. They are very small things that don't do much, but they are good at making your cell do things for them. Lines of code could refer to genetic material but that's not a good measure of how many functions it could execute.

I'm not aware of any effort to put viruses on a scale like this

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u/Dirty-Soul Oct 07 '22

To incoherently elaborate, using some of my own anecdotes from my brief time working in the field...

HIV uses a single strand of RNA to encode two different proteins - GAG and GAGPOL. One is basically a truncated version of the other, but they serve different roles in capsid formation, and are required in different ratios. (19:1, if you want the exact ratio of GAG to GAGPOL)

These two genetic regions are separated by a -1 frameshift site which turns 1 in 20 of all readthroughs into GAGPOL, whilst the remaining 19 in 20 terminate prematurely. This allows the virus to code for two proteins with just one open reading frame.

Seems complicated, right? It kinda is. Our genomes don't pull this kind of stunt because they don't need to optimise as much to survive.

So if you were to just measure "lines of code" or "number of open reading frames," it doesn't really convey the complexity of the behaviours which can be taking place. Complexity is a subjective measurement which relies on too many variables to make any meaningful comparisons.

To give another example, a tulip's genetic code is factors larger than that of humans. Are tulips more "complicated" than humans? Food for thought.

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u/xixouma Oct 07 '22

Thanks for contributing to the discussion, don't really have time to go in this much detail

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u/katarh Oct 07 '22

Coming at it from a comp sci perspective: Complicated code isn't always better. In any given programming language, there are about ten different ways to make the code do something. Often the simplest version is the best, because it's the way that introduces the least possible mistakes.

I would imagine it is the same for genetic information.

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u/Dirty-Soul Oct 07 '22

In genetics, it isn't always so clean-cut. Sometimes, the simplest "code" is also the most error prone. Viruses are usually as simple as possible, but they have extremely high levels of mutation because they make so many mistakes and don't have a proofreading step other than raw, elemental natural selection.

Evolution is a tinkerer which operates on a principle of iterative bandaids, duct tape and prayers. It doesn't "design" things in ways that make sense. So. you don't get a nice simple parallel between simplicity and reliability in the same way that you do for technology.

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u/Cogwheel Oct 07 '22

Evolution: Move Slow, Break Things

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u/NorthStarZero Oct 07 '22

Sounds like someone’s future PhD.

…just not mine.

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u/Longjumping_College Oct 07 '22

Is it important to solving long covid too? I'd imagine we need to figure out how to turn out back on to help those whose won't restart.

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u/xixouma Oct 07 '22

This is a difficult question which isn't addressed in this research, but it could be. Unfortunately science is done by small incremental steps and this is one of the first steps in this direction. We will need to find out if there is a link to long COVID. But some argue that long COVID is more due to hyperactivation of the immune system during infection which can cause damage long term

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u/SamTheGeek Oct 07 '22

hyper here being the opposite of non which this paper finds, right? There could be interesting ways of trying to use this immunosuppressive tendency against our own immune system to reduce post-acute symptoms if they are indeed caused by hyper activation.

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u/xixouma Oct 07 '22

I'm going to stress the point that there are different types of immunity, and the one they talk about in the paper is probably more related to intrinsic immunity rather than adaptive/systemic. They are cellular defense mechanisms rather than a whole system to protect a body

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u/SMTRodent Oct 07 '22

Not a virologist. CFS/ME often presents as 'long flu' - the 1980s name for it was 'Yuppie Flu' because it hit busy, hardworking active people the hardest (Yuppie meant 'young, upwardly mobile professional people.)

In all that time, no mechanism has been found, and no sign that a virus is still active in people who got flu and went on to get CFS/ME or in other words never recover.

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u/CronoDAS Oct 07 '22

There's a hypothesis that long COVID and other post-viral syndromes are basically autoimmune disorders; some of the antibodies or other defenses that the body made to attack the virus also end up targeting and doing collateral damage to healthy parts of the body.

(I wouldn't be surprised to find out that CFS is basically a neurological disorder. People studying ordinary muscle fatigue seem to have concluded that it's primarily a neurological phenomenon that doesn't have much to do with the actual muscle; in people who aren't athletes, the nerves start signaling fatigue long before the muscles come anywhere close to their actual physical limits, and people beginning strength training have rapid gains at the start because it recalibrates the nervous system's expectations to something more in line with what their muscles were actually already capable of.)

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u/sirrush7 Oct 07 '22

Now I'm curious... Is it the wild west sort of, with the levels and types of biohacking and reverse engineering that various virus do with our cells, or is it all roughly the same but to differing degrees.

Aaannddd: do you think we would ever come up with a medicine that is universal?

I am guessing not, if we've had to make vaccines to target different proteins and triggers on different diseases, it wouldn't be possible to make a sort of universal antidote eh?

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u/xixouma Oct 07 '22

it is the total wild west, nature is amazing at making new things...it's an endless pit of potential knowledge

Universal antiviral would be great huh. I feel like the best way to achieve this would be something that helps our bodies fight back, rather than targeted drugs. But some drugs out there affect a number of viruses, it's just uncommon.

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u/Dabier Oct 07 '22

In your opinion, what’s the “next big step” for antiviral medications? I know they exist but aren’t as effective as say antibiotics. Will they ever be that good?

Also, what’s your take on xlear/xylitol nose sprays? I was trying to look into how effective it was after I was exposed to Covid a while ago, but finding anything credible on it has been difficult for me.

Thanks!

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u/xixouma Oct 07 '22

Some nose sprays look promising, can't really advise anything medically but I think the approach makes sense. Some/many Antivirals are just as good as antibiotics, however they are almost always specific to a virus: they are designed to target specific parts of the viral life cycle, which is different for every virus. IMO next big step is modulating host immune processes to make your own body fight the virus better rather than just the drug. But it's just one avenue

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u/Dabier Oct 07 '22

Fascinating! Thanks for the reply!

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u/Nobrr Oct 07 '22

Hi, medchemist here. Antivirals generally:

  • affect viruses ability to interact with cells by targeting the virus

  • Prevent viral attachment and/or entry (endocytosis or phagocytosis)

  • Prevent replication of the viral genome .

  • Prevent synthesis of specific viral protein(s).

  • Prevent assembly or release of new infectious virions (exiting cells).

If we are talking covid, the best medications we could develop (outside of preventative vaccines) are those that significantly reduce symptoms (which does not reduce infection time) or specifically affect the viruses ability to replicate to reduce the duration of infection.

Antivirals are hard because viruses exploit cellular pathways that we generally require to live. Turning them off to stop a virus would mean death, so we have to be smart about it with selective deregulation or virus specific targeting.

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u/King_Pecca Oct 07 '22

I think I need to read a lot more about viruses, because everytime something like this pops up, I'm sure I don't really understand what viruses actually are.

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u/xixouma Oct 07 '22

Most people don't. There's a lot of resources I'm sure you could find at various levels of complexity. Do get educated, viruses are absolutely incredible things

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u/jadero Oct 07 '22

"This week in virology" is a great podcast. The format might not be for everyone, but it's jam-packed with goodies.

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u/YippieKiAy Oct 07 '22

What's your favorite flavor of ice cream?

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u/xixouma Oct 07 '22

Straciatella

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u/Long_jawn_silver Oct 07 '22

excellent choice

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u/SamTheGeek Oct 07 '22

I’m sorry, that’s a gelato.

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u/YippieKiAy Oct 07 '22

Yeah. I'm starting to doubt this person's qualifications. Anyone of the scientific community worth their salt would acknowledge the difference between ice cream and Gelato.

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u/productivehippie Oct 07 '22

Thank you for this comment. At first, this reads like SARS-COV-2 is a super virus to us lay people. I have always wondered if similar efforts in research and funding would be dedicated to other viruses at some point to show the similarities and differences between this virus and others (especially long-term effects). I just think that the attention of the media and the funding has been so heavily focused on SARS-COV-2 that this won’t be the case. What are your thoughts?

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u/xixouma Oct 07 '22

Some very good research groups are focused heavily on comparing viruses and how they affect us. SARS has also been beneficial in exposing just how much a virus can affect people long term and has spurred some more research on post-viral complications

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u/productivehippie Oct 07 '22

That’s encouraging then :) thank you!

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u/ShapersB Oct 07 '22

Do you have any pointers for how I can try to follow the ongoing research regarding post-viral complications? I’m currently dealing with long covid and I’d love to learn more about it. When I google i either find 1) sensationalized news articles or 2) way too technical research papers. Is there anything inbetween?

Regardless of if you’ve got time to respond to me, I’d also like to say thank you for taking the time to respond to the others. Making knowledge accessible is really important!

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u/[deleted] Oct 07 '22

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u/xixouma Oct 07 '22 Helpful

This will require further investigation

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u/Acceleratio Oct 07 '22

How are you doing today

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u/xixouma Oct 07 '22

Poorly actually, my cell culture died due to an incubator failure

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u/Acceleratio Oct 07 '22

I'm sorry to hear that

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u/SANPres09 Oct 07 '22

Let's all have a moment of silence for this cell culture.

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u/xixouma Oct 07 '22

Thanks guys

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u/Nemisis_the_2nd Oct 07 '22

I feel that pain. Hope it was something easy to set up and re-run again!

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u/Bobbias Oct 07 '22

Damn, you can't even learn anything from that (other than: don't use that incubator any more).

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u/Dirty-Soul Oct 07 '22

Just one more tragic victim of cancel culture...

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u/Smartnership Oct 07 '22

*canned cell culture

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u/Dirty-Soul Oct 07 '22

Ooh, I like this better.

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u/The_bruce42 Oct 07 '22

After all the variants over the past 2 years, how effective is the new vaccine? There has to be a dozen or so variants in different quantities around the globe.

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u/xixouma Oct 07 '22

Still very effective for what matters (in my opinion): mortality and severe disease. It seems increasingly less good at stopping an infection from happening, but has a dramatic effect on mortality and severe disease. The vaccine does try to target very conserved parts of the virus which it can only mutate so much. But you are right it's a bit scary how fast it's mutating

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u/NixonTrees Oct 07 '22

Should we take more precautions if we are just recovering from covid?

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u/xixouma Oct 07 '22

This isn't related to this paper in my opinion. But yes that's generally a good idea as viral infections can have lasting effects on immunity. This is also true for flu.

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u/[deleted] Oct 07 '22

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u/xixouma Oct 07 '22

I'm sorry to hear that. Seems to be a common experience unfortunately. Not enough is understood about this phenomenon really.

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u/vagabonne Oct 07 '22

What kind of precautions are you referring to?

On an unrelated note, what impact does Paxlovid have on this activity?

I know these questions don’t necessarily fit into your role, but I’m curious. I have COVID right now and had a much more severe version of it in January 2020 that had long-lasting effects, so I’d love to know what I should do now and should have done then.

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u/stokesetc Oct 07 '22

Could this lead to increases in Guillain Barre Sybdrome?

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u/xixouma Oct 07 '22

If SARS infection does increase the incidence of the syndrome then maybe this is a possible mechanism by which that could happen. I want to stress that this is not something the virus has just started doing. Its just that we now understand that it does this

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u/Overtilted Oct 07 '22

Are these mechanisms similar, or the same for other mamals?

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u/xixouma Oct 07 '22

Nice question. Good follow up study Idea. Could check in bats where the virus originated. One viral protein can have different functions depending on which host the virus infects. It's wonderfully complex

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u/SlickMcFav0rit3 Oct 07 '22

Given that ORF8 is divergent vs SARS1, I'd guess the virus picked the sequence up from either a host or another virus. Would be willing to bet that the mimicked H3 motif in ORF8 is conserved between bats and humans, though

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u/xixouma Oct 07 '22

That's a very good point. Agree on histone conservation in mammals for sure.

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u/AnaxImperator82 Oct 07 '22

I've always taken the bat origin as a fact without really understanding how they know. Now that you mention it here, which is the telltale sign of its bat origin? Is it possible to always tell from which species a virus originates?

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u/xixouma Oct 07 '22

No it isn't easy to tell from the virus itself wher e it came from. The best data is that you can find very, very similar viruses in bats. Follow Stuart Neil on twitter for some more advanced discussion on the topic

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u/gttmbrb Oct 07 '22

No question, just wanted to say that everything you said is super interesting!

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u/Omni33 Oct 07 '22

Is this a thing on newer mutations/variants or has it always been this way?

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u/xixouma Oct 07 '22

Good question. It would be possible to do an evolutionary analysis of sequences to find out if this gene has mutated a lot to evolve this function. I reckon that was it's primary function, as it is common for viruses to encode genes to divert our immune defenses. It is how they get past them and survive. Live hosts like humans are naturally very hostile environments to viruses, so they need to change them to be able to survive.

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u/marmosetohmarmoset PhD | Neuroscience | Genetics Oct 07 '22

Notice that this paper was originally submitted in December 2020, which means the research was done very early in the pandemic. That makes me suspect it’s not something only found in new variants.

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u/skkkkkt Oct 07 '22

HIV must be the perfect virus ( from a virus POV of course)

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u/xixouma Oct 07 '22

That's why I work on HIV! It is really good at hiding, something that SARS seems less interested in doing.

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u/skkkkkt Oct 07 '22

How’s it going so far? Any cure?

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u/xixouma Oct 07 '22

No actual cure. Very good treatment. Lifespan is unaffected by the virus if you are on anti-hiv drugs, you can't even spread it. People are working on a cure, I'm at a more basic and fundamental stage of research: how the virus evades immune defenses similar to that described in the article

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u/Med_vs_Pretty_Huge Oct 07 '22

As another virologist, my first thought seeing this post (OP's, not yours) was I would be more impressed to see a study showing a virus capable of causing disease in humans contains 0 proteins that turn off viral defense genes.

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u/Strongeststraw Oct 07 '22

Could this help explain why some people get so sick when others don’t? And maybe also explain the “super spreaders”?

That is, outside poor/harmful immune response and viral load.

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u/xixouma Oct 07 '22

Too early to say but it is possible this viral protein is more/less effective in some people that may have some genetic differences in the way they deal with this protein. Interesting question

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u/ThEtTt101 Oct 07 '22

Do we know why certain viruses, like covid for example, can jump easily from animals to humans and others can't?
Btw I've been reading your other responses and learning a ton, thanks for taking the time to do this, it's super interesting!

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u/xixouma Oct 07 '22

No problem. Yes some things are telltale signs of viruses with high zoonotic potential (keywords to Google if you want to read more). For example, is the entry receptor common in many species of animals including humans. Is the virus good at shutting down common defense mechanisms that are conserved in mammals for example. Interesting topic for sure

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u/Syndrome Oct 07 '22

I've heard that X% of our DNA includes parts from viruses (or something along those lines), not sure if it's true.

Could covid infections be making changes to our DNA, even if they're tiny? If not, do we know how the existing virus parts became part of our DNA?

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u/xixouma Oct 07 '22

Loads of our DNA is from viruses that infected "us" (as in infected Évry being at every stage of evolution that led to humans, from single cells to apes and us). The exact percentage is debatable but it's a huge amount. Most likely this viral DNA that is now ours (we actually use it to regulate our genes) came from viruses that integrate their DNA into ours such as HIV. They are called retroviruses. SARS doesn't do that, but who knows, maybe we will eventually pick up stuff from it.

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u/[deleted] Oct 07 '22

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u/xixouma Oct 07 '22

Hi, sorry can't give medical advice as I am not a medical doctor. I'm sorry to hear you are struggling, I hope you can find some support.

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u/lellers-all-the-way Oct 07 '22

Howdy, not addressed in this paper, but in your research do you have any idea how folks that are immuno compromised (pregnant women, new Borns, elderly, transplant patient etc) are impacted through this mechanism? My understanding is that pregnancy/new borns tend to not be impacted in any significant way (esp if vaccinated) by previous strains of the virus whereas the other groups can be hit particularly hard especially with other concurrent exacerbating conditions (clotting disorders, obesity, exacerbating inflammatory conditions etc). A lot of the original research focused on the other variants and I was just curious if the same standard could be applied to the new variants emerging, especially after elucidating this mechanism.

Since people are also vaccinated at different exposure times (different variants they’re exposed to)- does the effect of the vaccine on the the immune systems ability to “detect” this mechanism improve or worsen? Just curious, since the fall covid vaccines were updated (?) to match the changes in the patterns of mutations and was wondering if this kind of research was why.

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u/xixouma Oct 07 '22

So the type of immunity that I think this mechanism targets is quite different from those that immunocompromised patients usually have deficiencies in, it is called intrinsic immunity. I also want to point out that the mechanism elucidated in this paper is probably something that SARS has been doing from the start, even when it was still in bats.

Nevertheless it's a very interesting question which would have some clinical implications of any of your hypothesis are true. But I don't know if I'm honest.

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u/BimphyRedixler Oct 07 '22

Thank you for everything you do. <3

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u/AceOfRhombus Oct 07 '22

So basically we found out that it works like other viruses? Its not some crazy, new thing that we need to worry about?

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u/xixouma Oct 07 '22

Essentially yes, it's just viruses doing virus things. It is nothing to worry about, more to be excited about. We are finally learning why the virus is so good at infecting us, which could help us design drugs to hinder it!

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u/AceOfRhombus Oct 07 '22

That is exciting!! If you don’t mind, can I DM you about your career? Its similar to what I want to do with my degree

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u/xixouma Oct 07 '22

Yeah for sure

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u/Arcaneeff3ct Oct 07 '22

Honestly it’s so refreshing to see someone who loves their current job so much. I’m really happy you found your calling. I’d like to think I’m on a similar path and this just makes me happy.

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u/Cool-Specialist9568 Oct 07 '22

As a virologist, have the idiots of the past few years been...tough for you?

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u/xixouma Oct 07 '22 Silver Helpful All-Seeing Upvote

Look, in the end they aren't idiots. This is complicated stuff and science has a hard time explaining it to the untrained public. It's a big failure of science communication that so many people fall for misconceptions and conspiracies. I can't deny that it is frustrating anyways, but I am a scientist, and as such I don't have to interact with a great deal of people haha. Introverts unite

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u/LaughingHypocrite Oct 07 '22

Hello. That's exactly why I decided to become a science communicator. There are big ruptures between the general public and scientists. It's very interesting to see other people's thinking patterns. After all, at the end of the day, they just were failed by the educational system. Thanks for actually doing science!

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u/AceOfRhombus Oct 07 '22

Disregard the other comment, you made sense here! Maybe rupture wasn’t the best choice but your idea got across :)

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u/Reid22 Oct 07 '22

Love the humble response and your time to answer every questions. Thank you so much.

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u/light_at_the_end Oct 07 '22

You're a good person.

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u/m0nkeybl1tz Oct 07 '22

Sorry I’m confused, people in this thread are responding as if this disabling of viral defense is permanent and explains why people are getting viruses months later. Is that true, or is it a temporary effect around the initial infection?

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u/triffid_boy Oct 07 '22

I've not yet read the paper fully, so take this with that in mind.

This is through a mechanism used by cells to alter expression via epigenetics, so the changes could be longer term, in those cells that were infected. But viruses don't really leave cells alive, so it would be surprising if it was having a long term effect on the whole organism.

So, it should be a temporary effect.

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u/bandanagirl95 Oct 07 '22

It should be temporary, but that also wasn't part of the scope of this paper. Even further beyond the scope is how temporary "temporary" would be in that circumstance and if there are factors which could prolong or shorten it

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u/iankeetk Oct 07 '22

Yes, agree. Can it be said that RNA encoding the protein which mimics histone remains inside and translates afterwards? (I know this is not discussed here, but just asking)

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u/aquarianseawitch92 Oct 07 '22

I believe it’s possible but as commenters said above it’s likely very temporary because what typically happens in a cell infected with a virus is that the cell dies.

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u/BelovedApple Oct 07 '22

Could this be why I went 4 years without getting a cold but after getting COVID, I've had like 5 in 6 months

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u/turquoise_amethyst Oct 07 '22

Same. And it used to take 3-5 days to recover, now it’s more like 7-10 days. It’s like my immune system was “reset”.

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u/m0nkeybl1tz Oct 07 '22

It’s possible, but also remember that 2+ years of masking meant we were exposed to much fewer germs overall, and now that masking restrictions are being lifted and people are going out more you’re more likely to get “regular” sick again. It’s also possible that our immune systems are weaker from not having to deal with infections for those 2+ years, or it may be weakened due to the stress of 2+ years living through a global pandemic.

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u/Katana_sized_banana Oct 07 '22

This would explain some long COVID as for example the heart cells are very slowly replaced. A quick google says only about 1% per year. So if COVID infected the heart and permanently altered those, I mean it's just my layman theory, this could leave a lot of room for a long lasting effect of constant virus infections? We're constantly attacked by viruses from the environment and if they can always quickly infect the heart, this could explain stuff like fatigue even years after COVID.

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u/ForgedByStars Oct 07 '22

I think what triffidboy is saying is that once a virus infects a cell, it stops functioning as a normal cell and just creates new virus particles. Once it has created enough, the cell splits open and dies.

So once your body has defeated the virus, none of the surviving cells would have been infected.

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u/piecat Oct 07 '22

But what about dormant viruses? Like shingles from chicken pox? How on earth does that work?

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u/CrimsonFlash Oct 07 '22

They're usually in stasis, hiding in parts of the body that white blood cells don't go, such as the nervous system.

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u/SlickMcFav0rit3 Oct 07 '22

Viruses that can become latent are usually DNA based or retroviruses, so they can hide in the nucleus

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u/Exaskryz Oct 07 '22

Not all viruses hijack the cell and make it exclusively produce more viruses. The cell's usual DNA is still around and a cell will ry its best to continue to function. Remember, viruses and cells have no intent. They just biochemically react. Whatever DNA or RNA is around, its proteins work on that.

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u/Whole_Suit_1591 Oct 07 '22

Genes turn on and off for different reasons. What happens in a truly healthy person may be totally different in a immuno-compromised person. Chicken or the egg scenario I would think.

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u/01-__-10 Oct 07 '22

It’ll take effect as long as the ORF8 protein persists in the cell. Probably as long as active viral replication is ongoing, and maybe a little while longer. Depends on the half life of the protein.

The changes enacted on chromatin, and therefore gene expression, would last longer still, and I could only speculate how long they might persist.

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u/bandanagirl95 Oct 07 '22

The paper specifically looks at the action during infection. It didn't look at how long it takes the defense to recover or if fragments of RNA could stick around coding for the proteins involved (and subsequently how long they would stick around)

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u/SlickMcFav0rit3 Oct 07 '22

A lot of the experiments aren't in the context of infection, they're over expressing a tagged version of the viral protein... So even harder to figure out what would happen in a person

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u/ManOfDiscovery Oct 07 '22

It’s a temporary effect during the infection associated with a particular mutation that increased severity. Anyone claiming otherwise or giving anecdotes are Lyme Diseasing what’s actually being talked about.

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u/Premed_with_a_2_GPA Oct 07 '22

Lyme Diseasing

Meaning?

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u/cjbest Oct 07 '22

Many people attribute their problematic health conditions to past Lyme infections without evidence that Lyme is capable of long-term health impacts.

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u/artdco Oct 07 '22

There’s actually good evidence that Lyme infection can affect one’s long-term health if one has it for a while before diagnosis/treatment. However, there are a lot of people who attribute symptoms to “chronic Lyme” when there’s no evidence they ever had Lyme in the first place. This is troubling because one of the “treatments” prescribed by clinicians who diagnose “chronic Lyme” in these patients is long-term, heavy-duty antibiotics, which can have their own serious negative health impacts. I get the appeal of it all: it’s psychologically difficult to cope with unexplained symptoms, and the medical establishment can be dismissive! But unfortunately these folks aren’t getting treatment for whatever is really making them sick, in addition to the risks of unnecessary treatment for “Lyme.”

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u/IRNotMonkeyIRMan Oct 07 '22

I'm wondering the same thing myself.

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u/Irisgrower2 Oct 07 '22

I'm not r/Manofdiscovery so I don't know their use of the term but at the risk of Lyme Diseaseing a definition of "Lyme Diseaseing" I'll give it a shot.

I grew up not far from Old Lyme Connecticut. When the panic of a tick born illness finally started going public, getting coverage, folks flipped out. When my mom hit a deer in the car her chief worry was tick flew off, through her open window, and landed on her. Fields or scrub brush were being burned due to "infestations".... and the rub is Lyme was only antidotal symptoms at that point. Nothing was truly verifiable, it was all subjective, except for the bulls eye bite mark. It was a Karen illness. Eventually folks were reporting the same symptoms who were not within similar, pre Internet, social networks. The catch, it hit folks in both diffent ways regarding severity. This ment data could begin to be agrigated. It took years and years of data. Out of all that came what we know of as the list of Lymes symptoms. Until then it was winey tinfoil hat folks.

So....the definition for "Lyme Diseaseing" could be claiming scientific fact based on broad, publicized, subjective experiences.

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u/DaemonKeido Oct 07 '22

So to make this as basic as possible, This mutation is what makes the side effects of infection worse with COVID. Does this mutation activate every time infection occurs?

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u/Cleistheknees Oct 07 '22

Nothing in this paper suggests histone modification persists past the infection. However, a basically permanent residence of viral genomes inside cells isn’t without precedence: all HSVs, EBV, HIV, etc are all basically lifelong infections, though obviously with very different severities of outcome.

The reality is that even if you got it on January 1st of 2020, we’re not even three years from that point yet, which is well within the range of persistence we see from other viruses. Probably more relevant is that for many people, this is the first severe respiratory virus they’ve experienced. Talk to anyone over 60 who has been hospitalized with bacterial pneumonia or the like, and you will find recovery times well over a year, probably in most of them. Getting really, really sick has a physiological toll and I think a lot of “long-haulers” are (understandably) looking for an unnecessarily complex explanation for something that is frankly not an unusual outcome of severe infectious disease.

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u/SlickMcFav0rit3 Oct 07 '22

Long term persistent infections are rare for RNA viruses. The viruses you mentioned are DNA viruses (HIV is an RNA virus that is reverse transcribed into DNA)

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u/4-Vektor Oct 07 '22

Is that mechanism similar to what the measles virus does?

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u/eniteris Oct 07 '22 edited Oct 07 '22

If you are referring to the "immune amnesia", then no, SARS-CoV2 has not been shown to have that ability. Immune amnesia seems to be caused by the viral envelope, whereas this is a protein produced inside the cell.

EDIT: alright it looks like the amnesia comes from the virus infecting the memory B- and T- cells and killing them all off.

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u/TrivialBanal Oct 07 '22

That's a relief. That's the one virus weapon we don't want them sharing around.

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u/CaptainTarantula Oct 07 '22

Is that common in nature?

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u/James_Camerons_Sub Oct 07 '22

How would a coronavirus develop this ability? Aren’t viruses primarily looking to evolve to infect as many hosts as they can without fun, added features?

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u/pursnikitty Oct 07 '22

Measles has the ability to cause immune amnesia and even make it harder for the immune system to respond to new pathogens in the future. So there’s a not-so-novel virus that’s been adding fun new features.

Also about 8% of the human genome is made up of viral dna. With more under suspicion.

Viruses love inserting their junk all over the place.

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u/mschuster91 Oct 07 '22

Measles has the ability to cause immune amnesia and even make it harder for the immune system to respond to new pathogens in the future.

Is the mechanism that causes this known? Would be nice to replicate this artificially without bone marrow transplants - at least people with severe autoimmune diseases or multiple highly sensitive allergies could benefit.

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u/DrShrime MD/PhD | Health Policy | Global Health Oct 07 '22

Fun fact. There’s a fascinating disease called noma that is theorized to start because other viruses, like measles, make the immune system forget how to keep the normal bacteria in someone’s nose / mouth in check

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u/Duckfoot2021 Oct 07 '22

They don’t “look” for anything with intention. There’s just so many that random mutations find vulnerabilities in the host—some helpful, some not. But there’s nothing “intentional” about the process.

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u/triffid_boy Oct 07 '22

Suppressing a viral response is very much an advantage to the virus. So, it evolved.

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u/ExaBrain PhD | Medicine | Neuroscience Oct 07 '22

Evolution is not teleological - it's not a process with a goal or outcome in mind. It's just a case of variation amongst a population and the more successful variations carrying on a prospering while the less successful ones are outcompeted and die out which is what we call natural selection. Viruses are mindless and have no goal, it's easier to think of them as little machines which reproduce and evolution just means that they get better at it over time by what ever changes show an advantage to the population.

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u/sklzthtklz Oct 07 '22

This assumes a virus has an active role in its own development, when in reality it either benefits the virus to do so (future infection possibly) or actually provides no benefit to the virus at all, but doesn't cost it anything to have. The hairs on our arms serve no purpose except to fall in my spaghetti when I'm cooking sometimes, but we have them because not having them provides no distinct advantage. Quickly changing viruses are a shotgun of genetic variation, stuff that has no purpose gets carried along on an otherwise successful virus.

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u/ExaBrain PhD | Medicine | Neuroscience Oct 07 '22

Remembering of course that arm hairs are a vestigial remnant of when we had full hair like any other primate that we used to keep warm. While the massive reduction in hair density was likely driven by the need to exert ourselves in high temperatures and optimise sweating, we still have them as there is neither benefit or deficit for keeping them.

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u/Petersaber Oct 07 '22

or deficit for keeping them.

They sometimes tickle and make my brain think there is a colossal spider on my arm.

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u/GReaperEx Oct 07 '22

But if you didn't have them, you would be less likely to feel an actual spider on your arm. They provide the extra tactile sensation which is otherwise absent for most of our body.

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u/ExaBrain PhD | Medicine | Neuroscience Oct 07 '22

Contrary to popular belief, vestigial does not mean useless. The appendix has some use in providing a protected biofilm of good gut bacteria in the event of some major illness that affects the rest of the gut and in detecting foreign infectious agents in food despite it no longer being the massive cellulose digesting structure that it once was.

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u/Petersaber Oct 07 '22

There is only one way out of this. Develop spider forcefields.

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u/Reagalan Oct 07 '22

you should find a colossal spider and play with it so you know what it feels like.

tarantulas are cute

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u/Listen_for_chains Oct 07 '22

Or maybe a side affect from eating arm hair spaghetti!!!

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u/justabill71 Oct 07 '22

Ah, yes, of course, the al dente variant.

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u/MessoGesso Oct 07 '22

It calls for elbow macaroni

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u/nerd4code Oct 07 '22

Evolution can work surprisingly fast and effectively—think of it as the totality of life-as-it-exists learning how to survive indefinitely into the future. It uses (basically) universe-noise to probe the solution space, and even if the fitness function gets stuck in a local extremum for a while, as long as one organism can hop out and survive long enough to reproduce, that stickyness won’t be permanent. Virus strains “can” even “sample” DNA or RNA from multiple host species, and end up mixing and matching capabilities to arrive at tricks that humans wouldn’t easily cogitate their way to. For some algorithms, evolution can even offer a stochastic circumvention of NP-hardness, which is not quite as sexy as it sounds… still impressive, though.

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u/Charming_Cheetah_117 Oct 07 '22

There is this debate about whether evolution just leads to continual "improvement" or if it's mostly adaptive and speeds up when the environment changes. The latter is called "punctuated equilibrium", and it makes a lot of sense to me.

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u/VorAbaddon Oct 07 '22

This would in theory mean it takes longer or forever for our body till it without defenses.

Its like a crook who wants to steal being able to turn off the cameras. Would make it harder to catch them.

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u/nikeler Oct 09 '22

As someone currently ill with "something " and testing negative...

I MUST remind everyone that the newer variants are also evasive to the home tests (at least)

You may test negative repeatedly and STILL HAVE COVID.

Please wear a mask when in public access places.

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u/Trurorlogan Oct 07 '22

Interesting for sure! I wonder how temporary this really is. If it acts like a herpes virus and stays in the organism, i could see this being permanent or intermittent?

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u/Jayer244 Oct 07 '22

It's very temporary and can't be compared to the herpes virus inactivity. Supressing the immune system is something that nearly every virus does. Even the flu has genes that supress the cells response to an infection

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