In fact they're so absurdly specific that while you could bathe in a solution of them and not get sick, they also frequently fail to infect slightly different members of the same species, which is why ultimately they never become antibiotic alternatives: having the right one on hand ranges from difficult to impossible.
Viral infections only successfully persist by replicating faster then the human body destroys them, and by hiding in human cells.
This isn't a system which is some sort of toxic to viruses, it's an immune booster.
And, yes, it needs to be applied before symptoms start to appear. Otherwise death is almost for certain.
I doubt this research will lead directly to a better vaccine, but having a better vaccine could save a lot of lives.
Given that the article goes on to talk about mild persistent inflammation, is it possible that these individuals are sometimes asymptomatic but still capable of carrying/transmitting viruses at least temporarily? The article talks about potentially immunizing healthcare workers during a future pandemic, but if this was just allowing people to never develop symptoms (and not have to leave work) while having low-grade infections, would we accidentally create a work-force of Typhoid Marys?
It seems that the goal is to learn to trigger the benefits, without triggering the bad parts. Which, should probably have been obvious to you without even bothering to read the article.
https://www.frontiersin.org/journals/immunology/articles/10....
While I was looking for the reference above this also came up:
https://www.sciencedaily.com/releases/2020/02/200210144854.h...
when bat cells quickly release interferon upon infection, other cells quickly wall themselves off. This drives viruses to faster reproduction
Quite a way from whole-animal physiology in the referenced research, by all means, but it's a fair point, right.
> “In the back of my mind, I kept thinking that if we could produce this type of light immune activation in other people, we could protect them from just about any virus,” Bogunovic says.
This sounds terrifying. There's a reason our bodies do not regulate like this.
I can't remember which series it was, though.
>Bogunovic’s therapy is designed to mimic what happens in people with ISG15 deficiency, but only for a short time.
Given the choice between 2 weeks of a moderate COVID infection (fever but no hospitalization), and 2 weeks of this therapy, I would guess that the moderate COVID infection gets you at least 10x the inflammation.
But the article didn't talk about imposing constant low-grade inflammation. In fact, they specifically said they were talking about 3-4 days.
This was a lynch pin of sorts in Koch's postulates. We can't properly go through those postulates with viruses like we can with biological pathogens, but it is odd to me that we don't have similar concerns when the presence of a replicable pathogen doesn't cause the symptoms they are expected to cause.
I know as a health care worker I actually think about things like this. MRSA is a good example. Most people don't react to exposure but some do. Those that do get long term infections that are hard to get rid of if ever. Most think of this as a hospital issue. But the reality is that there are literally thousands of people with MRSA all over the world and they are carriers of it and they do things like go to the bank machine and touch it, open the door at 7-11, pick up items at the store and then put them back on the shelf and so on and so on. MRSA is literally everywhere. Some people contact it and suffer problems others do not.
That the root of the confusion for me. I haven't wrapped my head around how we can know a specific pathogen causes disease if a large number of people can be found to have that pathogen present without showing symptoms.
Not all smokers get lung cancer. But with large enough samples, smokers turn out to be much more likely to get lung cancer than non-smokers. That's why we say that smoking causes lung cancer. It's not as if someone has actually watched a particle of tobacco interact with someone's lung cells to turn them cancerous in real time.
Contagion would mean that the smoke can infect the host, replicate, and spread to others. That's not how second hand smoking works.
I have encountered side effects that probably no one has seen before, simply because of rarity and peculiarity of behavior. You don't run into a ton of people using both interferon and doing karate, so if bruising more easily happens 10% of the time... would anyone notice?
Personally I would be more worried about persistent inflammation causing inflammatory disorders, of which there are many. If there are like 10,000 individuals with this trait then there just aren't enough to detect. But that seems direct... wouldn't you expect something like this to potentially even destroy viral reservoirs over time?
The fact that this is short term in the treatment made me 1000x more comfortable with the idea in any case.
(I may have watched too much House)
Oh, and here's what the ISG15 deficiency (the condition these mRNAs are there to simulate) does:
> Patients present...with infectious, neurologic or dermatologic features. Basal ganglia calcification is observed in all patients... The basal ganglia calcifications may cause epileptic seizures... The IFN-I inflammation may also manifest early in life as ulcerative skin lesions in the armpit, groin and neck regions. Finally, ISG15-deficiency leads to mendelian susceptibility to mycobacterial disease... [t]hese infections present as fistulizing lymphadenopathies and respiratory symptoms following BCG vaccination.
Yeah, about those antiviral superpowers...
His reputably published, peer reviewed, work can be found here: https://www.science.org/doi/10.1126/scitranslmed.adx5758
Among the symptoms of this disease includes things like necrotic lesions and severe multi-systemic damages.
From what I gather the fact that these people are not more susceptible to viral infections was a surprise. Which probably relates to why the doctors in the parent article were investigating its possible anti-viral properties.
Just like you accept the risk of increased yeast infections while treating bacterial infections with antibiotics, or the risk of any infection while treating a cancer with chemotherapy.
There seems to be a lot of information, misinformation, conspiracy theories, and information hiding at least in the perception, if not in reality.
I cannot imagine what society at large will have to deal with or what the reaction will be for or against an “everything” therapy, given what happened with Covid.
The biggest negative effect is i've been hearing "you'll be dead in six months from this vaccine" for about 5 years now.
It's been 5 years. have you nothing else going on in your life?
The information has not changed dramatically since a few months after its release, and the myocarditis risk was not detected in clinical trials because it is an unbelievably rare event. Detecting it would've required trials orders of magnitude larger than any clinical trial ever.
My summary for programmers:
When you get a viral infection, immune cells make a signalling protein called a IFN-1 (Type I Interferon) cytokine, and this flips a boolean flag to True on a bunch of genes (interferon-stimulated genes or ISGs) that produce a bunch of proteins (hundreds) that control the infection. ISG15 is one of them and its role appears to be to downregulate and to limit the inflammation.
The paper title refers to a ISG15 deficiency, meaning if you are dificient in ISG15 that inflamation limitation goes away. But the paper is actually about how in people that naturally have a ISG15 deficiency, there is an always-on low level expression of some of these pro-inflamation genes. So they take that as a safe level.
The did RNA sequencing on experimental ISG15 deficient cells and from heatlhy individuals, identified the mutations, narrowed down to 10 genes (antiviral ones not inhibitors) that in combination significantly inhibited viral replication. They stuck the RNA for such genes in lipid nanoparticles such that they enter host cells, whose ribosomes happily read the RNA like a turing head reads a tape in base 20 and produce proteins encoded by these genes, similar to how the mRNA vaccine works.
So why not dose with the IFN-I directly? Three referenced papers show its "poorly tolerated with significant side effects" and all those downregulators that get expressed limit the inflammation response.
Disclaimer: IANAB (not a biologist) corrections might be due..
I think we'll never have this "one shot," but continue to find tailored treatments for individual conditions. There's no way out of this complexity with "one simple trick," which seems really appealing to the people who determine what gets popular in social media and seemingly politics now. Its just going to be boring and grueling academia and medical trials that are hard for the layperson to understand, hence the important of funding these programs. The recent right-wing election wins and thus a right-wing government cutting all manner of medical grants is supported by the "one weird trick" crowd. Hopefully, the USA will have better leadership in the future to get us back to actual science and to find actual new treatments.
Already, even on HN, the top comments are conspiracy-culture coded, "but, but this one company bought the patent and disappeared with it!" Sigh.
""" In March 2024 Kimer Med announced it has signed a contract valued at up to USD$750,000 (NZD$1.3 million) with Battelle Memorial Institute (Battelle), the world’s largest independent, nonprofit research and development organization. The contract is focused on the discovery and development of new antiviral drug candidates for the treatment of alphaviruses. """
https://en.wikipedia.org/wiki/History_of_virology#Discovery
Hippocrates could recommend elderberry for a bunch of ailments, but he didn't have the concept of a "universal antiviral".
The miracle of the mRNA covid vaccine and the use of that framework to treat cancer is a good example.
As we wind down research in the US, there will be lots of churn as the market finds new approaches to development.
DRACO "is a chimeric protein with one domain that binds to viral double stranded RNA (dsRNA) and a second domain that induces apoptosis when two or more DRACOs crosslink on the same dsRNA." (Ridder et al 2011). This article is about packaging mRNA for a set of 10 interferon-stimulated genes that express multiple proteins that target various stages of viral replication.
And there's not even the only one (there are other syncitins).
Disclaimer: I'm not a medical professional
Eliminate human-tropic viruses: We have to monitor for outbreaks when new viruses mutate and jump species to successfully infect humans. If there's zero mass immunity across the population at every outbreak, we're still in a high-risk situation.
* An increase in autoimmune diseases (related to the hygiene hypothesis).
* Decreased resistance to future viral pandemics, since the body wouldn't have practice since childhood in fighting viral disease.
It could be chaotic, I think.
https://m.youtube.com/watch?v=SbvAaDN1bpE
Are we also eliminating transposons? We would not survive that.
Not saying this isn't worth researching but I'd expect big question marks around risk/reward.
I wonder how different it is from interferon therapy - interferons are used to signal viral infection, so they also activate immunity.
giancarlostoro•5mo ago
I'm genuinely asking, I'm a simple software dev not a doctor.
kristjank•5mo ago
busyant•5mo ago
FWIW, I was trained as a bacterial geneticist and routinely used bacteriophage (viruses that infect bacteria) with various resistance mutations.
Viral mutations are not restricted to viruses that infect bacteria.
edit: in fact, fundamental aspects of the genetic code were determined by analyzing and exploiting viral mutations.
https://en.wikipedia.org/wiki/Crick,_Brenner_et_al._experime...
busyant•5mo ago
The Crick, Brenner et al. paper that I cited above
* studied mutations in a viral gene called "rIIB"
* the authors used those rIIB mutations to determine that the genetic code was a non-overlapping triplet (now called codons) -- a pretty fundamental discovery.
* What's amazing to me is that they still have NO IDEA what the rIIB gene actually _does_, mechanistically.
It's like learning a little bit about God using an enigma machine (sorry, shitty simile).
thyristan•5mo ago
And bacteria self-replicate, whereas a virus needs to infect a cell and be reproduced by that cell. Some antiviral mechanisms attack the reproduction proteins that the human cells use, which the virus cannot do without. And the human cells don't have reproductive pressure to replicate viruses, quite the contrary.
francisofascii•5mo ago
strbean•5mo ago
I think the biggest difference is that bacteria can react to a treatment, while viruses don't have the capacity to react. If you've stopped a virus from replicating, it's essentially dead. A bacterium may have defensive measures it can take. It could form an endospore and try to wait things out. If you've stopped it from reproducing, as it ages it might start accumulating free radicals that increase DNA damage, leading to a higher chance of it mutating to resist the antibiotic. Etc.
Terr_•5mo ago
Bacteria also swap genes between themselves [0], whereas two viral particles sitting on the same Petri dish are too inert/simple for that. That represents an additional way for adaptive tricks to spread.
https://en.wikipedia.org/wiki/Horizontal_gene_transfer
jojobas•5mo ago
aredox•5mo ago
2) To further illustrate, some viruses have been nearly eliminated with a single vaccine. Polio didn't manage to adapt before going almost extinct. And a good reason why is:
3) Viruses can only evolve inside contaminated hosts. If you find a cure that stops quickly the virus from multiplying and contaminating, you are also curtailing its ability to adapt. A contaminated host is a giant casino machine, allowing the virus to mutate until it hits a new evolutionary step. A strong enough vaccine or treatment is like throwing out the virus before it has time to play much.
tialaramex•5mo ago
mschuster91•5mo ago
And even worse, some viruses can swap genes if a host has multiple infections at a given time. Bats in particular are known as "hot pots".
grapesodaaaaa•5mo ago
XorNot•5mo ago
tiahura•5mo ago
And no, strep throat is not worse than ebola.
bee_rider•5mo ago
There’s some ambiguity in their comment because it isn’t obvious what we’re sort of… averaging over, but I think they clearly don’t mean that there no serious viral infections exist.
ted_dunning•5mo ago
The examples that you gave that I checked were not supportive of your assertions.
grapesodaaaaa•5mo ago
What I was trying to ask is if you took pre-antibiotic staph and resistant staph, rolled back in time and infected two people, would one be worse than the other?
ie - are they harder for the immune system to fight, or just resistant to antibiotics.
quotemstr•5mo ago
But so what? Anti-pathogen drugs are useful in the period during which resistance hasn't become universal, and if and when it comes a problem, we'll have other drugs.
Besides: sometimes you get lucky and the virus goes extinct before it can develop resistance (e.g. smallpox)
MengerSponge•5mo ago
capitainenemo•5mo ago
glenstein•5mo ago
It's an extreme example, but it demonstrates a fundamental constraint that can't be evolved around. Ideally vaccines can find an equivalent in the space of mechanistic interactions that cut off any evolutionary pathway a virus could reach, either exterminating the virus before it has enough time to complete the search, or by genuinely leaving no pathway even with infinite searching.
Contrary to what you may have heard from Jeff Goldblum life does not always find a way.
capitainenemo•5mo ago
MengerSponge•5mo ago
capitainenemo•5mo ago
There are indeed bacteria which can survive high bleach concentrations. It was a minor nitpick.
MengerSponge•5mo ago
But I bet if you weren't worried about etching or skin safety you could find a concentration that would handle those little buggers. It's the sterilization equivalent of "It can't be stuck if it's liquid"
etiam•5mo ago
And the really, really bad part about abusing natural parts if the immune system to provoke pathogen resistance against them is that the resistance will target part of natural immunity.
See also https://news.ycombinator.com/item?id=35700881
0xDEAFBEAD•5mo ago
etiam•5mo ago
Admittedly the method in the present article is probably better than the idiocy of extracting antibacterial peptides from context for use as drug products, since at least this will always be used in the context of a full immune system and they trigger a number of genes which probably regulate a whole subcomponent of measures rather than just one or two mechanisms.
Even so, it lifts up a particular part from the diffuse field of defenses as salient and particularly worthwhile to defeat.
Also, keep in mind that many species of virus have so small genomes they have to overload the readings of parts of the nucleic acid sequences to get a full set of proteins.
Evolve to evade the immune system, certainly. But if you're implying that it will happen in the same ways, at anything like the same rate and to the same extent regardless of what we do, no that's not right.
0xDEAFBEAD•5mo ago
By your logic, we'd be better off if we gave patients a cocktail containing small amounts of many different antibiotics. By giving a single antibiotic in a large dose, we are "lifting up a particular part of our field of defenses as salient and particularly worthwhile to defeat". Sounds bad.
Willing to bite the bullet and sign on to this kitchen-sink approach, of offering patients a cocktail containing small amounts of many antibiotics?
The problem I see with the cocktail approach is that a pathogen can gradually evolve defenses against everything simultaneously, in parallel. With a cocktail, every element of the cocktail provides a distinct glide path for a virus to increase its contextual fitness. That also sounds bad! The main way I see this situation improving is if two elements of the cocktail happen to act as a sort of clamp, where any virus which begins to defeat one ends up increasing the effectiveness of the other.
0xDEAFBEAD•5mo ago
Based on my recollections of this paper https://pmc.ncbi.nlm.nih.gov/articles/PMC5499642/
So yeah, I wouldn't be super worried about the virus evolving to become worse in absolute terms as a result of antiviral exposure. Virii are evolving all the time anyways. Antivirals can also reduce evolution speed by fighting an infection: A more severe infection means more virions means greater evolution speed. I believe some new COVID variants were thought to have evolved in the body of someone who was severely infected. (However: Note that it's not necessarily beneficial for fitness for the virus to evolve greater infection severity, especially if that interferes with transmission.)
tempestn•5mo ago
ted_dunning•5mo ago
I think (also without a citation) that this was never properly demonstrated.
And there is nearly nobody left who has no immunity from either infection or injection. We are definitely still seeing quite a few deaths from COVID.
tempestn•5mo ago
cwmma•5mo ago