Biology Evidence based Monkey Pox thread

[Skorpio]

If anyone would like to discuss the scientific literature around the Monkey Pox virus that is currently in the news.

The Monkey Pox virus is in the genus othopoxvirus which also contains smallpox and cowpox, its case fatality rate is significantly lower than that of smallpox but the symptoms are not nice. It is a pretty long (roughly 200 kb) dsDNA virus. DNA is more stable than RNA and double stranded is more stable than single, so this won't mutate as much as

There is a draft assembly here. This was taken from a single patient and sequenced using quite a noisy sequencing platform (ONT) to a depth of 7x. For a high quality assembly you want significantly higher than this, I'm not sure exactly how much is required for a linear genome with (presumably) little repetitive content, but the depth is likely an order of magnitude lower than it should be. The low coverage means that the reference used for this assembly will heavily dominate. In regions of low coverage the consensus sequence will just use the corresponding sequence from the reference genome.

A high quality assembly will be a good first step to understanding this virus from a genomic perspective, as is the case for any virus.

Comparing the basic stats, it is quite similar to Variola (smallpox) in terms of length and GC content. I just ran pyfastx stat on the reference genome provided by the link above and the refseq for variola. There is currently no refseq for the monkey pox virus (taxid 10244) but if this becomes a thing that will change. There are some references on the NCBI database, but the most recent is from 2018 (virologists have had attention elsewhere....).

Right now its just watch this space in terms of whether we should be worried. I'm gonna say no given its mode of transmission....

---

I'm going to paste in this article from the journal Nature to spare the paywall.

This article does a good job at summing up what we currently know about the viral structure, the symptoms and the big question of why it has spread the way it currently has.

Monkeypox goes global: why scientists are on alert​

Scientists are trying to understand why the virus, a less-lethal relative of smallpox, has cropped up in so many populations around the world.
More than 120 confirmed or suspected cases of monkeypox, a rare viral disease seldom detected outside Africa, have been reported in at least 11 non-African countries in the past week. The emergence of the virus in separate populations around the world, in locations where it doesn’t usually appear has alarmed scientists — and sent them racing for answers.

“It’s eye-opening to see this kind of spread,” says Anne Rimoin, an epidemiologist at the University of California, Los Angeles, who has studied monkeypox in the Democratic Republic of the Congo for more than a decade.




The virus is called monkeypox because researchers first detected it in laboratory monkeys in 1958, but it is thought to transmit to people from wild animals such as rodents or from other infected people. In an average year, a few thousand cases occur in Africa, typically in the western and central parts of the continent. But cases outside Africa have previously been limited to a handful that were associated with travel to Africa or with the importation of infected animals. The number of cases detected outside of Africa in the past week alone — which is almost certain to increase — has already surpassed the total number detected outside the continent since 1970, when the virus was first found to cause disease in humans. This rapid spread is what has scientists on high alert.

But monkeypox is no SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, says Jay Hooper, a virologist at the US Army Medical Research Institute of Infectious Diseases in Fort Detrick, Maryland. It doesn’t transmit from person to person as readily, and because it is related to the smallpox virus, there are already treatments and vaccines on hand for curbing its spread. So although scientists are concerned — because any new viral behaviour is worrying — they are not panicked.
Unlike SARS-CoV-2, which spreads through tiny air-borne droplets called aerosols, monkeypox is thought to spread from close contact with bodily fluids, such as saliva from coughing. That means a person with monkeypox is likely to infect far fewer close contacts than someone with SARS-CoV-2, Hooper says. Both viruses can cause flu-like symptoms, but monkeypox also triggers enlarged lymph nodes and, eventually, distinctive fluid-filled lesions on the face, hands and feet. Most people recover from monkeypox in a few weeks without treatment.

On 19 May, researchers in Portugal uploaded the first draft genome of the monkeypox virus that was detected there, but Gustavo Palacios, a virologist at the Icahn School of Medicine at Mount Sinai in New York City, emphasizes that it’s still a very early draft, and more work needs to be done before any definitive conclusions can be draw


What researchers can tell from this preliminary genetic data is that the strain of the monkeypox virus found in Portugal is related to a viral strain predominantly found in West Africa. This strain causes milder disease and has a lower death rate — about 1% in poor rural populations — compared with the one that circulates in Central Africa. But exactly how much the strain causing the current outbreaks differs from the one in West Africa — and whether the cases popping up in various countries are linked to one another — remains unknown.
Answers to those questions could help researchers to determine whether the sudden uptick in cases stems from a mutation that allows monkeypox to transmit more readily than it did in the past, and whether each of the outbreaks traces back to a single origin, says Raina MacIntyre, an infectious-diseases epidemiologist at the University of New South Wales in Sydney, Australia. Unlike SARS-CoV-2, a rapidly evolving RNA virus whose variants have regularly eluded immunity from vaccines and prior infection, monkeypox is caused by a relatively large DNA virus. DNA viruses are better at detecting and repairing mutations than RNA viruses, which means it’s unlikely that the monkeypox virus has suddenly mutated to become adept at human-to-human transmission, MacIntyre says.

‘Deeply concerning’​

Still, for monkeypox to be detected in people with no apparent connection to one another suggests that the virus might have been spreading silently — a fact that Andrea McCollum, an epidemiologist who heads the poxvirus team at the US Centers for Disease Control and Prevention in Atlanta, Georgia, calls “deeply concerning”.

Unlike SARS-CoV-2, which can spread without causing symptoms, monkeypox does not usually go unnoticed when it infects a person, in part because of the skin lesions it causes. If monkeypox could spread asymptomatically, it would be especially troubling, because it would make the virus harder to track, McCollum says.

Another puzzle is why almost all of the case clusters include men aged 20–50, many of whom are men who have sex with men (MSM). Although monkeypox isn’t known to be sexually transmitted, sexual activity certainly constitutes close contact, Rimoin says. The most likely explanation for this unexpected pattern of transmission, MacIntyre says, is that the virus was coincidentally introduced into an MSM community, and has continued circulating there. Scientists will have a better idea of the origin of the outbreaks and the risk factors for infection once an epidemiological investigation — which can take weeks and involves rigorous contact tracing — is complete.

Containment strategies​

Scientists have been keeping an eye on monkeypox ever since an eradication campaign for smallpox, a closely related virus, wound down in the 1970s. Once smallpox was no longer a threat thanks to worldwide vaccinations, public-health officials stopped recommending smallpox inoculation — which also kept monkeypox at bay. With each year that has passed since smallpox’s eradication, the population with weakened or no immunity to these viruses has grown, MacIntyre says.

There have been a few monkeypox outbreaks since then. The Democratic Republic of the Congo, for example, has been grappling with the virus for decades, and Nigeria has been experiencing a large outbreak, with over 500 suspected and more than 200 confirmed cases, since 2017, when the country reported its first case in some 40 years. The United States also reported an outbreak in 2003, when a shipment of rodents from Ghana spread the virus to pet prairie dogs in Illinois and infected more than 70 people.
Public-health authorities are not powerless against monkeypox. As a precaution against bioterrorism, countries such as the United States maintain a supply of smallpox vaccines, as well as an antiviral treatment thought to be highly effective against the virus. However, the therapies probably wouldn’t be deployed on a large scale to tackle monkeypox, McCollum says. Health-care workers would probably instead use a method called ‘ring vaccination’ to contain the spread of the virus: this would vaccinate the close contacts of people who have been infected with monkeypox to cut off any routes of transmission.
On the basis of the data that she has seen so far, McCollum thinks the current outbreaks probably won’t necessitate containment strategies beyond ring vaccination. “Even in areas where monkeypox occurs every day,” she says, “it’s still a relatively rare infection.”
doi: https://doi.org/10.1038/d41586-022-01421-8

 

[Jabberwocky]

following from the portugeuse assembly, i had some more time to look into this today. there is a french draft sequence here:

https://virological.org/t/first-french-draft-genome-sequence-of-monkeypox-virus-may-2022/819

at first glance it looks like it would be higher quality. they claim a depth of 38x, still too low for real SNP calling. whoever did their DNA extraction and library prep needs the sack. Of 7.9 million reads, only 12918 mapped to their reference. And their average fragment size was 700 bp. Function hell. ONT can go up to 10s of kb quite easily. I think most of the contamination was human, but i have never seen a sample that has this amount of host contamination. i've only seen clinical samples from covid patients though so maybe there's some fundamental difference here.

they provide their analysis pathway, very standard. pretty low effort assembly.

there is also a german one here:
https://virological.org/t/first-ger...ted-to-multi-country-outbreak-in-may-2022/812

this is based on illumina reads so more likely to be appropriate for SNP calling. they don't give any information regarding average depth coverage so can't be sure. again use very standard tools, but at least they used an actual assembler rather than just doing a reference based consensus (i.e. what the french and portugeuse ones did).

assuming that they had high enough coverage for SNP calling to be remotely appropriate, the following is interesting:
The full-length genome comprises 197.378 bp and was sequenced directly from clinical material. BLAST analysis [3] and phylogenetic inference support the classification of this isolate into the West-African clade associated with the recent isolates from Europe and the US. The nearest neighbor is PT0010/2022, an isolate from Portugal (published May 23 by INSA). All of the identified SNPs compared to the MPXV_UK_P2 22 are either TC→TT or GA→AA in dinucleotide context and potentially caused by APOBEC3 as hypothesized by Rambaut 15. In addition, a 10 bp deletion (CAATCTTTCT) was discovered at 133.175 bp which is part of an exact tandem repeat or an inexact triplet repeat upstream of a hypothetical protein. Interestingly, this duplication is not annotated in the recently published CDC strain ON563414 38 and the Belgium strain ITM_MPX_1_Belgium but in all sequences from Portugal (PT0001-PT0009).

In English, for the conspiracy theorists: WE DO NOT HAVE A HIGH QUALITY REFERENCE GENOME YET. so any musings about a cover up or whatever are premature, we'd need a high quality sequence before it was worth putting a load of N's in

Also, biorXiv only has 55 hits for 'monkeypox,' i'll start thinking its a thing if this number starts increasing switfly.

 

[Snafu in the Void]

Pet hamsters belonging to monkeypox patients should be isolated or killed, say health chiefs

Fears grow that the virus could become endemic across Europe if it makes the jump to animals

www.telegraph.co.uk

Pet hamsters belonging to monkeypox patients should be isolated or killed, say health chiefs​

Pet rodents – including hamsters, gerbils, guinea pigs and mice – are considered most at risk, as they are known to be susceptible to the disease.

“Rabbits and mice would be ones to watch, as they’re likely to be kept as pets,” Dr Robertson said, pointing to a 1976 study which concluded they can catch the virus.

“This virus does have quite a wide host range which is always worrying in terms of potential to establish in a new host species… it would seem sensible to monitor any animals/pets that infected people are in contact with,” he added.



Brief history of monkeypox


1970
The first case of monkeypox in a human was recorded that year in the Democratic Republic of the Congo.

2003
The disease was detected in the US when an outbreak occurred after rodents were imported from Africa.

2018
The first-ever cases in the UK were detected, when three people contracted the virus following contact with a man who travelled back from Nigeria.

2019
Another case in the UK was recorded in London in Dec 2019, and a further two cases were detected in north Wales in 2021.
All of the infections were believed to have been caught by travellers who had been to Nigeria.

 

[Jabberwocky]

one new paper added, taking biorXiv hits to 56:

Scrutinizing surface glycoproteins and poxin-schlafen protein to design a heterologous recombinant vaccine against monkeypox virus

Monkeypox is a zoonotic disease caused by monkeypox virus with noteworthy mortality and morbidity. Several recent outbreaks and the need of dependable reconnaissance have raised the level of concern for this developing zoonosis. In the present study, a reverse vaccinology strategy was developed...

www.biorxiv.org

its about a vaccine design. not my area of expertise, don't know the research group involved or where they've submitted it, so can't comment on the scientific merit.

 

[Jabberwocky]

what should be a reasonable assembly has been posted:

Illumina whole-genome sequence of Monkeypox virus in a patient travelling from the Canary Islands to France

Gregory Destras1,2,3, Antonin Bal1,2,3, Bruno Simon1,2, Quentin Semanas1,2, Hadrien Règue1,2, Bruno Lina1,2,3, Laurence Josset1,2,3 GenEPII Sequencing Platform, Institut des Agents Infectieux, Hospices Civils de Lyon, F-69004, Lyon, France Laboratoire de Virologie, Institut des Agents...

virological.org

they took 84M illumina paired end reads. for illumina, the reads are almost perfect except towards the end of read 2. so this is a much more suitable platform for assembly than ONT. they also have 950x coverage which is higher than necessary and should yield a pretty much perfect assembly. it is not clear why they built 4 sequences, or whether these are all based on the same read sets. but the sequences agree almost perfectly.

as mentioned in the comments, there is some disagreement between these sequences and other 2022 assemblies. these are at the ends of the genome in highly repetitive regions. if these regions are longer that the 2x250bp (illumina reads are usually 250 bp and these are paired end)+ the insert size (distance between the reads, as they are taken from opposite ends of a DNA fragment) then it makes sense that illumina reads were not able to resolve these regions well, even with their insanely high coverage. they did a fudge of allowing reads with mapping quality 0 (usually meanng that the reads map to multiple places in the genome) to be used in their assembly to recover the SNPs that were present in the other 2022 sequences.

i really don't know why, with this number of high quality reads, they went for reference based rather than de novo assembly. de novo should easily be feasible with that coverage, though they ould still struggle with the repetitive end regions unless they supplemented the illumina PE reads with something that gives longer range info, like LMP.

full sequence here: https://www.ncbi.nlm.nih.gov/nuccore/ON622722.2?report=fasta not a single N, conspiracy theorists gonna need to try harder. the totality of difference to the 2018 sequences seems to be ~50 SNPs (in nearly 200,000 bases) and one short deletion.

 

[Jabberwocky]

two more papers have been posted:

https://www.biorxiv.org/content/10.1101/2022.06.18.496696v1 looks interesting, i need to give it a proper read. would be good to see the functional role of the protein they highlight.

and a genomic analysis: https://www.biorxiv.org/content/10.1101/2022.06.01.494368v2 thta tbh looks like the bare minimum tbh- compared to a few other monkeypox genomes and then other species from the same genus using standard tools. not read the full paper, but if they do some functional prediction of the amino acid variants they identify then that raises the standard of the paper.

i think at this point we can conclude fairly positively that this wll not be a thing.

 

[Neuroborean]

. I think most of the contamination was human, but i have never seen a sample that has this amount of host contamination.

can you explain this further, please?

 

[Jabberwocky]

I think that really doesn't say too much about it since the 2018 strain could be an engineered one (or not) without the specific pieces that would make it more transmisible.

do you have any evidence for this? there isn't a single 2018 strain, in fact most of the reference based assemblies use different references, which is bonkers imo.

there may have been some functional analysis on the role of those SNPs by now but when i posted there was no discussion about their potential role. i'm not even sure how well the monkeypox genome is understood. interestingly, this paper from 2014 mentions a deletion that "seems to" (because their p isn't below the arbitrary 0.05 cutoff) correlate with human-human transmission. it doesn't include full genomic analysis- just PCR of selected regions. either way i wouldn't be surprised if the deletion mentioned in that paper is the same deletion seen in the more recent sequences

this isn't dated but going by the url i'd guess its from late may, but there is no mention of what the SNPs might do: https://ncbiinsights.ncbi.nlm.nih.g...ses cluster into,to-human spread is suspected.

can you explain this further, please?

i meant they badly fucked up their library prep (the process that takes a thing containing genetic material and extracts that genetic material and prepares it for sequencing). clinical samples always contain cells from the patient,that is literally how they are collected, so some human DNA is inevitable.

my own experience with clinical samples in this context is quite limited, but i do know the lab guys fucking killed it at purification/host removal, because human DNA content was very low in the data i was given. my lab know their shit, but the above was taken at a hospital, if they are routinely doing this type of analysis then its mind boggling that they haven't sorted out their library prep to remove this. sequencing is expensive (even when using ONT, if you're sequencing a bunch of useless host DNA every time, costs will mount up), so they are wasting huge amounts of resources sequencing human DNA when their aim is to sequence viral DNA, and this could probably be avoided. i say probably because there may be some technical reason why its more difficult in the case of monkeypox..... thouh i doubt it cos none of the other sources posted have this level of contamination. i

 

[Neuroborean]

do you have any evidence for this?

Come on, we need evidence of course,
but we also need some EXPLANATIONS about why the fuck Bill Gates was warning us about a pox pandemic and why there was another (another because Clade X and Event201 existed) tabletop exercise in 2021 depicting basically all that is happening. Do you really believe in coincidences at this point?
I do not.
What I mean is that they could basically throw around those animals with monkeypox in USA in 2018 to make everyone unsuspicious of a new clade/strain of engineered smallpox, I certainly would have done that.

In anycase I think this is more transmissible because of the covid vaccine damaging the immune system (CD8 ) There's enough evidence about that, please don't make me gather that information (I already did in a telegram group but not in the PC) as it can be easily retrieved googling or using better search engines.
You probably think this is not real but I can tell you that at the end of the year the virus will be completely "installed" in society and the "measures" are going to start again. Finally they'll blame someone, bioterrorists or the "russians",
this message stays here so you'll can see how true or false it is.

mod add: this was deleted by the user because 'rules' yet they kept other posts that similarly contravene them. i (chinup) would like this to stay because firstly, if you dictate 'this message stays here' then it should stay and secondly, i would like this to be an example for others led down anti-science paths, to see in 6 months time when none of these predictions come to pass.

 

[Jabberwocky]

Come on, we need evidence of course,

sooooo.... you don't have evidence and instead think a conspiracy argument holds weight?

what does 'What I mean is that they could basically throw around those animals with monkeypox in USA in 2018 to make everyone unsuspicious of a new clade/strain of engineered smallpox' mean? you do realise that monkey pox and small pox are different species, right? they are in the same genus. but are you claiming that the monkeypox going around currently is an engineered smallpox? it really is not.

this message stays here so you'll can see how true or false it is.

you don't get to make that call. i'll leave it because i have a suspicion you'll regret posting it in 6 months time but this is not the type of discussion S&T is for.

having posted something somwhere completely unrelated is not an excuse not to post it again, evidence your claims. a quick search suggests nothing even vaguely substantiating your claim, despite detailed studies in this area, such as: https://www.nature.com/articles/s41586-021-03841-4

please read the S&T posting guidelines and keep your conspiracies to the dive and the lounge.

 

[Neuroborean]

that monkey pox and small pox

Do you realize that when they did the tabletop exercise or whatever the heck it was with monkeypox, right?
it doesn't matter at all if Gates said smallpox a few months before if his Foundation was completely into the spot when they did the exercise in Germany, they obviously knew what's going on.

https://www.nti.org/news/nti-bio-munich-security-conference-convene-global-leaders-annual-tabletop-exercise-reducing-high-consequence-biological-threats/

https://www.nti.org/wp-content/uploads/2021/11/NTI_Paper_BIO-TTX_Final.pdf

This guy was there:
"Dr. Chris Elias President, Global Development Division Bill & Melinda Gates Foundation"

I don't why what's wrong with you guys (scientists) that you always prefer to look somewhere else instead of recognizing that SOME people, SOME scientists are not good people.
That wouldn't hurt science, but good scientists looking somewhere else and denying the most scandalous stuff really harms science as a whole. To be scientific is to never deny anything that is possible till it's completely demonstrated that is not the case, as you surely know there's also the falsifiability principle.

I'm not saying the monkeypox is engineered smallpox, you're saying that to create confusion in the post, which is not nice. If there's a strain that has not been problematic and then a new similar strain appears then the typical reaction would be "ok, nothing new...". If you engineered a virus but you don't "finish" it so it remains not very transmissible then you just need to finish the last proteins (those that would make it more transmissible) and it could seem "natural", till they find the details, which is going to take time, based in the fact that the 2018 strain seemed to have a natural origin and wasn't very transmissible.

I have an hypothesis, that can be obviously proven wrong in the next months, it really is more a probability based forecast. Smallpox vaccines are going to be used against monkeypox (we already know that), that vaccines wouldn't be problematic if the people injected didn't have a fucked up immune system. As they have a fucked up immune system some people won't be able to control the infection of those modified vaccinia ankara viruses and then real smallpox is going to start.

 

[Jabberwocky]

Do you realize that when they did the tabletop exercise or whatever the heck it was with monkeypox, right?

its not relevant. these sorts of things happen all of the time, its part of being prepared for possibilities. if you hold a couple such events a year, chances are that when a virus hits the news, one of the exercises performed over the past few years will have been for that type of threat.

you always prefer to look somewhere else instead of recognizing that SOME people, SOME scientists are not good people.

how is this relevant to our discussion? also, i've not made this claim. in fact over the course of the past few years i've bitched endlessly on here about my old boss who is neither a good person nor a good scientist despite being highly respected in his field. i never claimed that scientists don't do anything nefarious, that would be ludicrous, they're people.

I'm not saying the monkeypox is engineered smallpox, you're saying that to create confusion in the post, which is not nice. If there's a strain that has not been problematic and then a new similar strain appears then the typical reaction would be "ok, nothing new...". If you engineered a virus but you don't "finish" it so it remains not very transmissible then you just need to finish the last proteins (those that would make it more transmissible) and it could seem "natural", till they find the details, which is going to take time, based in the fact that the 2018 strain seemed to have a natural origin and wasn't very transmissible.

i asked what you meant by your statement 'What I mean is that they could basically throw around those animals with monkeypox in USA in 2018 to make everyone unsuspicious of a new clade/strain of engineered smallpox' apologies for misinterpreting, i still don't understand what that statement means.

you do realise that from 2019 virologists and people with literally any relevant skills were moved straight onto covid work? in fact, most had to be to keep working in the initial lockdowns cos if you weren't doing something directly relevant to fighting covid you weren't even allowed into your lab cos the work was deemed inessential. they have not had time to fanny about with other viruses. over the past year yes, but 2019-2020 no.

with the amount of sequencing currently being done of monkey pox patients we will soon see which portions of the genome are highly conserved and which regions can yield mutations that are strongly positively selected for. we'll be able to watch it evolving in real time, like we did with covid (here is a lovely tool for tracking sars-cov2 evolution). if someone were to sneak in something that made it significantly more transmissible, it would almost certainly stick out like a sore thumb, especially given its such a long dsDNA virus so has a low mutation rate. the proteins affecting transmissibility will be more likely to vary so its natural that we'll see more mutations there, which means that researchers will focus on that region, making anything nefarious even harder to hide at this point.

I have an hypothesis, that can be obviously proven wrong in the next months, it really is more a probability based forecast. Smallpox vaccines are going to be used against monkeypox (we already know that), that vaccines wouldn't be problematic if the people injected didn't have a fucked up immune system. As they have a fucked up immune system some people won't be able to control the infection of those modified vaccinia ankara viruses and then real smallpox is going to start.

vaccina is not variola. so this hypothesis doesn't make sense to me. and you still have not substantiated your claim that covid vaccines have wrecked people's immune systems.

 

[Neuroborean]

vaccina is not variola. so this hypothesis doesn't make sense to me. and you still have not substantiated your claim that covid vaccines have wrecked people's immune systems.

I perfectly know that vaccinia is not variola, is better to use vaccinia cause its risks are less severe but are quite severe on those individuals with compromised immune systems. Nonetheless:

Side Effects of Smallpox Vaccination | Smallpox | CDC

Side Effects of Smallpox Vaccination

www.cdc.gov

"

• Buildup of inflamed tissue around the vaccination site that may at first look like a bullseye and will grow into a large, non-healing sore (known as progressive vaccinia). This usually happened to people with a deficient immune system.
• Inflammation of the brain (known as postvaccinal encephalitis).

People with certain medical conditions—including people with weakened immune systems or certain skin conditions—are more likely to have these reactions and should not get the smallpox vaccine unless they have been exposed to smallpox. You can read more about people who should not get the smallpox vaccine in Smallpox Vaccine Safety."

I already told you that I don't waste my time "substantiating my claims" gathering information that is open for everyone, as I told you I already did, in a telegram group, I've been working on this for years, I don't think it's right to do extra effort for people who are closed in advance to consider certain possibilities. Seriously, I need to prepare a master thesis so my time is quite compromised.

i asked what you meant by your statement 'What I mean is that they could basically throw around those animals with monkeypox in USA in 2018 to make everyone unsuspicious of a new clade/strain of engineered smallpox'

Ok, my bad, normally we talk about pox as a general disease/family of viruses, that's why I meant by smallpox (pox or pox-like)

its not relevant. these sorts of things happen all of the time, its part of being prepared for possibilities. if you hold a couple such events a year, chances are that when a virus hits the news, one of the exercises performed over the past few years will have been for that type of threat.

Do you say this seriously?
So you think it's likely that there's a preparation for a hypothetical coronavirus pandemic and some months after we have one and now the same thing would happen with monkeypox (a virus that barely had any pandemic risk compared to other viruses) and you consider that normal?
I don't know exactly what is your "anomaly threshold" but surely this beats all my standards, and most people standards.

 

[Jabberwocky]

then real smallpox is going to start.

I perfectly know that vaccinia is not variola,

so how is a different virus going to start 'real smallpox?'

I already told you that I don't waste my time "substantiating my claims" gathering information that is open for everyone,

then you should stop posting in S&T as it is a requirement here. any further unsubstantiated claims will be removed to ensure posts meet the guidelines. if its so easy for people to verify themselves, then its even easier for you to drop a few links in your posts and we would be less likely, as i did, to stumble on huge amounts of material completely contradicting your claims while attempting to validate them.

Do you say this seriously?
So you think it's likely that there's a preparation for a hypothetical coronavirus pandemic and some months after we have one and now the same thing would happen with monkeypox (a virus that barely had any pandemic risk compared to other viruses) and you consider that normal?

i say it completely seriously.

look, in my job we frequently talk about how we would engineer a bioterrorism attack, exactly what we would do, how we would spread it etc. if there is a bioterrorism attack that i haven't written down in my notes somewhere as a possibility then i've failed. does that mean, when such an attack happens, that i was involved in the conspiracy? no. the same goes for these guys. if a possibility that you haven't considered, when doing that is part of your fucking job, then you sucked at your job. all you're saying is that the people running these events don't suck at their jobs.

 

[Neuroborean]

then you should stop posting in S&T as it is a requirement here. any further unsubstantiated claims will be removed to ensure posts meet the guidelines.

I'll do it on my own, thanks,

in anycase you'll see the reality sooner than later,

 

[Jabberwocky]

ohhhhh..... we are up to 69 papers on the biorxiv. i'm now quaking in my boots. not really. these slower ones are likely to be of slightly higher quality than the earlier ones because some time was put into their preparation.

i've only read the abstracts of these two, they're in my wheelhouse, this one says nothing new but they probably put more time into validating, which means we can be surer of previous claims of the same:

Genomic analysis of the recent monkeypox outbreak

The Monkeypox virus is the etiological cause of a recent multi-country outbreak, with nearly one hundred distinct cases detected outside the endemic areas of Africa in May 2022. In this article, we analyze the sequences of two full genomes of Monkeypox virus from Portugal and Belgium, and...

www.biorxiv.org

regarding the amino acid changes, these quotes are relevant:

'A42R is a short (~130 aminoacid long) protein homologous to eukaryote profilins, actin-binding proteins involved in cytoskeletal structure and function, such as membrane trafficking'

though it doesn't mention endocytosis so might not be that meaningful. maybe @Skorpio could comment cos this is the edge of my biology.

'Orthopoxvirus 324 amino acid long glycosiltransferase located on the viral envelope, which plays a role in the attachment to the human target cell and in the general poxvirus entry [26]. We considered H3L due to its pivotal immunological importance, since it offers one of the main epitopes recognized by the host immune system [27]; studies showed how antibodies elicited by smallpox vaccines are binding H3 proteins [28], with specific recognition of H3L as an antigen by immune CD8+ T cells'

relates to why they are planning to use smallpox vaccines for this.

this one is more about provenance:

Genomic regions insertion and deletion in Monkeypox virus causing multi-country outbreak-2022

The genetic diversity and evolutionary origin of the Monkeypox virus (MPXV) that is currently creating a multi-country outbreak-2022 is not fully understood. Here we report that the MPXVs that cause outbreak-2022 (MPXVs-2022) have deletion/insertion of ∼500 to 2000bp nucleotide in multiple...

www.biorxiv.org

its interesting that they are mentioning large insertions when none of the earlier assemblies that i posted in this thread contain them. i might take a look at the assembly they used tomorrow.

 

[Skorpio]

Ok I'm going to run through some of the cell biology of viruses, both to situate anybody reading this on the same plane and to arrange my thoughts. I'm going to use italics for the more background material and go back to normal when I begin to address @chinup's question.

Viruses are simple pathogens which use a large amount of their host cell's machinery to replicate themselves and spread. A virus particle contains the genetic material of the virus (DNA, or RNA) and coat proteins which both package the genetic material and facilitate interaction/uptake with new target cells.

The (non)-life cycle of a virus begins with the uptake of a viral particle into a host cell. This occurs by the binding of a virus surface protein to some surface protein in the cell, often either a receptor (as receptors get internalized due to activation) or a protein involved in an endocytocis process (endocytocis is how cells consume elements "outside" of themselves. Simplifying the process, the cell membrane will grow around what it is about to take in until the particle to be taken in is surrounded by membrane and brought into the cell).

Once inside of the cell, the virus will break association with its binding partner and release it's genetic material. This will be replicated by polymerase enzymes in the host cell and transcribed to RNA (if the virus uses DNA as it's material), which is then turned into viral proteins.

Now viruses have optimized for efficiency of their coding, so pretty often they spit out their proteins connected together so that a single ribosome will produce all of the viral proteins like sausage links still connected by their casing, except for a processing one which is produced on its own. This processing protein will trim the proteins apart making them functional.

These functional proteins can then package the viral genetic material into the coats and the viruses are ready to infect new cells once the current host cell blows open from all the virus inside it being made.

The protein in the monkeypox virus (which is common to many poxes) resembles the human protein profilin. Profilin binds to the actin cytoskeleton of cells and influences the dynamics of the actin filaments. Actin is a small protein like a lego brick that can be stacked top to bottom. Actin filaments are constantly growing at top end and falling apart at the bottom end. Proteins that regulate these relative rates control the shape of the actin cytoskeleton.

Importantly actin growth is what mediates endocytocis. By using a viral protein to trigger endocytocis without needing to bind to a receptor enzyme, the virus can infect a broader range of cells (all plant and animal cells use actin as a key structural protein).

This paper demonstrates that the viral profilin proteins alone will be taken up by human cells via endocytocis.

This of course is likely quite an incomplete description of the viral entry process. The mentioned H3L protein likely works in tandem with the profilin by binding to specific sugar residues on human cell surface proteins, tethering the virus in proximity to the cell long enough for the profilins to exert their action and for the virus to not float away during the process of endocytocis.

 

[Jabberwocky]

The protein in the monkeypox virus (which is common to many poxes) resembles the human protein profilin. Profilin binds to the actin cytoskeleton of cells and influences the dynamics of the actin filaments. Actin is a small protein like a lego brick that can be stacked top to bottom. Actin filaments are constantly growing at top end and falling apart at the bottom end. Proteins that regulate these relative rates control the shape of the actin cytoskeleton.

Importantly actin growth is what mediates endocytocis. By using a viral protein to trigger endocytocis without needing to bind to a receptor enzyme, the virus can infect a broader range of cells (all plant and animal cells use actin as a key structural protein).

thank you so much for this detailed post and providing the background for those that find it useful, i'm woefully bad at doing it.....

we actually seem to be quite lucky that given it can infect basically any cell type, it seems pretty bad at doing it. i don't think the world is ready for another virus spread easily by respiratory droplets. i guess if smallpox had been more contagious we wouldn't have survived as a species.

 

[Neuroborean]

thank you so much for this detailed post and providing the background for those that find it useful, i'm woefully bad at doing it.....

we actually seem to be quite lucky that given it can infect basically any cell type, it seems pretty bad at doing it. i don't think the world is ready for another virus spread easily by respiratory droplets. i guess if smallpox had been more contagious we wouldn't have survived as a species.

You can see the "trend" of spread, doubling up in numbers more or less each 10 days...

Mpox

Explore data on confirmed mpox cases and deaths.

ourworldindata.org

with the same trend (which is not guaranteed, obviously) it will reach 21 million cases in about 3 months.

 

[Jabberwocky]

You can see the "trend" of spread, doubling up in numbers more or less each 14-16 days...

Mpox

Explore data on confirmed mpox cases and deaths.

ourworldindata.org

with the same trend (which is not guaranteed, obviously) it will reach 21 million cases in about 3 months.

that is def an exponential curve if ever i saw one, but where are you getting 21 million in 3 months?

3 months = ~ 14 weeks. so going by doubling every 2 weeks, we have 2^7, current rate is ~500 per day so projection for 14 weeks time is 500*(2^7) =64000. i can't be bothered to integrate properly so lets assume its the maximum daily case rate applies for every day of the next 3 months (approx 93 days), a very obvious over estimate. but that would give ~ 6 million cases. many fewer than 21 million cases. i totally believe that humans are horny enough to fuck their way into exponential growth of a virus.

i haven't got the formula exactly right cos i'm basing off rough memoy of how to do these calculations, but if you apply the same rule for the data on the graph, june 4th is 70 cases, 3 doubling periods later on july 14th we have ~510. 70*(2^3) = 560 so an over estimate but not way out. i guess what i'm saying is unless i'm being really thick, which honestly is a possibility, i can't see how you'd get 21 million cases projected based on that graph.

bioarxiv is up to 72 hits for monkeypox. as a proxy for interest in academia, i'd say this mean no1curr.