Thread by @VBruttel

DID THE MONKEYPOX (MPXV22) OUTBREAK COME FROM A LAB?
location, transmissibility, number and type of mutations strongly suggest so😬

disclaimer: this is a PRELIMINARY analysis, a first look, an invitation to an open discussion,🙏rt!
I hope to be wrong.
But the data...😱
a🧵
1/x

Disclaimer 2:
Please leave all your
-ad hominem/you're not a virologist
-monkeypox is harmless
-but some expert said something else
-you're a conspiracy theorist
-first prove it 100%
arguments at home.
Point out
-analytical mistakes
-opposing data
-better explanations
please!
2/x

Let's get to the facts:

1) LOCATION
The case numbers suggest that the MPXV22 outbreak started in Europe, likely in the London area: There was one patient who travelled from Nigeria, but he was isolated and his contacts traced.
All others outbreaks started in Africa.
3/x

2) TRANSMISSIBILITY
MPXV22 rapid spread is highly unusual.
Increased transmissibility can be explained by prolonged spreading among humans (which wasn't observed, neither were intermediate strains) or e.g. lab experiments such as passaging with human cells.
4/x

3) NUMBER OF MUTATIONS
DNA viruses usually mutate very slowly, accumulating 1-2 mutations/year. This MPXV22 mutated 6-12x faster, which AFAIK has never before been observed in nature.
(sources of many following statements:
virological.org/t/discussion-o…
researchsquare.com/article/rs-170…)
5/x

THREAD UPDATE!
Dear all, in the original thread I pointed out MPXV22 had a VERY specific mutation pattern which is typical for APOBEC enzymes (90% GA➡️AA/TC➡️TT), which are identical rev. complements).
Labs e.g. in London were using APOBECs to hypermutate e.g. wt HIV.
new6/x

But, as @babarlelephant and @halvorz pointed out, I was focussing on the wrong APOBEC/mutation pattern (A3G), AND this very specific mutation pattern had been observed before. Thanks a lot!
➡️I had to correct that part, sorry!
In fact, this pattern first emerged 2017 in MPXV.
7/x

In this graph, the ratio of mutations almost certainly caused by an APOBEC is indicated by the color, and you can see that some MPXV strains suddenly started accumulating up to 100% APOBEC mutations.
@babarlelephant thinks this is caused by a mutation or a new host (humans?).
8/x

@babarlelephant However, MPXV has infected humans for decades, and some daughter strands seem to mutate randomly again (blue lines on the right), which speaks against a viral mutation.
So what else could cause this APOBEC-hypermutation profile?
Hypermutation therapies? APOBEC-boosting drugs?
9/x

MPXV is currently rapidly spreading among men having sex with men.
Quite a few cases had concomitant HIV co-infections.
And activating hypermutation therapy of HIV by activating APOBECs/inhibiting HIVs VIF could induce such a pattern in co-infecting MPXV.
See RN-18.
10/x

There are also other, similar compounds.
Not sure how careful they'd design a hypermutation trial if they claim APOBECs hypermutate genomes from Glycine to Alanine (amino acids) instead of from guanine to adenine (nucleotides)...
11/x

so let's sum this up:
MPXV22 has a new, very specific hypermutation profile typical for human APOBECs.
MPXV patients often also have HIV.
Some developmental (?) HIV hypermutation inducing drugs activate/shield APOBECs.
Was MPXV22 caused by therapeutic hypermutation trials?
12/x