Immediate PB2-E627K amino acid substitution after single infection (...) | Hacker News Reader

Immediate PB2-E627K amino acid substitution after single infection (...)

virologyj.biomedcentral.com

14 pointsgreenavocado22 comments

I've flagged this submission. The title is editorialized and indicates an event occurred which didn't (or at least is not supported by this paper). The South Korean lab did not make bird flu 100% lethal, they studied an in-the-wild bird flu and ran experiments on mice.

The event as in the research has occurred, and it was 100% lethal to all mammalian subjects and also the conclusion of the research is that the pathway would be applicable to all mammals.

So a lab in fact has created a highly contagious flu virus (far higher than regular flu) through gain of function research which has indeed killed 100% of the subjects which contracted it even if they were only mice.

> So a lab in fact has created a highly contagious flu virus

This paper does not appear to support that. They indicate the source was an existing, in the wild virus.

>> We isolated an HPAI H5N1 clade 2.3.4.4b virus from wild birds in Korea with 96% E and 4% K at amino acid position 627 of PB2. To investigate the genomic characteristics of this clade regarding mammalian adaptation, we studied the replication and transmission of the H5N1 virus in mice.

That was the gain of function research.

They infected mice with a wild strain that already was pre-positioned to better infect mammals used super high viral loads for that then watched as the mutations which promote mammalian infection evolved and exposed challenge mice to the newly developed strain.

After reading the abstract, this title seems to me like flame/click-bait.

This test has been done in mice only (since no other animal was mentioned in the abstract).

If one follows the scientific method, this means whatever conclusion the authors make can only be extended to mice. Extrapolation to “mammals” is not present in the abstract implicitly or explicitly.

> Two experiments with different challenge-to-contact ratios were conducted to assess transmission dynamics and mutation development. In experiment 1, a 4:1 challenge-to-contact ratio resulted in 100% transmission among direct-contact mice, with all mice succumbing to the infection. In experiment 2, a 1:1 ratio yielded 50% transmission, with all challenged mice also succumbing.

It’s not clear from the abstract that any human-made changes were made to the H5N1 either.

The paper is interesting, but it doesn't seem to be supporting your title? I'm just past the part where they showed 100% infection rate in mice.

> resulted in 100% transmission among direct-contact mice, with all mice succumbing to the infection.

I thought so too, but later on in the paper they mention that they performed necropsy on the mice that survived.

> samples from surviving mice on day 12 were also obtained through necropsy to measure viral titers.

Not only that, but just a month earlier, South Korean scientists published another Virology Journal paper revealing that they had engineered a chimeric H5N1 virus using hallmark gain-of-function (GOF) techniques, combining gene segments from three different influenza viruses to increase the virus's heat resistance, alter host targeting, and enhance human cell entry.

"Recombinant viruses were generated using a pHW2000 plasmid-based reverse genetics system."

"Combining the R90K and H110Y mutations (22W_KY) resulted in a synergistic increase in thermal stability and maintained HA activity without measurable reduction even after 4 h at 52 °C."

"22 W HA and 22 W NA genes, along with six internal genomic segments (PB2, PB1, PA, NP, M, NS) from PR8 and a PB2 gene from 01310 containing the I66M, I109V, and I133V (MVV) mutations"

The study also confirmed enhanced antigen uptake and intracellular penetration in human cells:

"The highest level of intracellular entry was observed for BEI_22W_KY, confirming its superior effectiveness in penetrating cells."

Ref: https://virologyj.biomedcentral.com/articles/10.1186/s12985-...

> In experiment 1, a 4:1 challenge-to-contact ratio resulted in 100% transmission among direct-contact mice, with all mice succumbing to the infection. In experiment 2, a 1:1 ratio yielded 50% transmission, with all challenged mice also succumbing.

What's not supported from the title is that they only tested in mice. But they do keep mentioning "mammalian adaptation" so it might just be that it's expected all mammals to suffer the same fate without certain adaptations.

What could possibly go wrong?

The next era of MAD won't be with bigger bombs but with bio-weapons. Easier to disseminate, potentially deadlier than an entire arsenal of nukes, and maybe even more selective if it can be designed to be targeted or only one side has the vaccine.

We have been told our whole lives that nuclear winter will be the end of humanity, but in reality, biomedical scientists will exterminate us.

Everyone knows that such bioweapons cannot be contained, which is why they don't get used. Vaccines are very problematic because they don't reliably work for mutations, and have side effects of their own.

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