https://t.co/DF40S9biYF
Unfortunately the observed ORF8 inactivation or the nsp6 SGF deletion are both indicative of T cell depletion, yet the deletion of HV and Y suggest functional B cell immunity—specifically the HV deletion is not observed in the patient nor the ORF8

@BallouxFrancois Deactivation. The nsp6 SGF is located in an ER exposed loop that is conserved even in long passage within immunocompromised patients. The loop likely interacts with nsp3 and help antagonizing cellular autophagy. And human-like B cell immunity does not cause deletion here.
@BallouxFrancois Cellular autophagy help display peptides on MHC class II molecules, and ORF8 removed MHC class I molecules. The loss of both functions suggest the host cytotoxic T cell immunity is not functional yet the S deletions are consistent with B cell immunity in an altered host
@BallouxFrancois Environment. As the long covid-associated immnocompromisation was not found to cause either SGF deletions (or any deletions) in ORF1ab nor does it inactivate ORF8, Cytotoxic T cells are functional enough in these patients to require both functions to remain intact.
@BallouxFrancois It can not be HIV since that https://t.co/yKJIxeSzlf depletes helper T cells instead of cytotoxic T cells https://t.co/h0aN2vnkLk ,ironically creating a patient condition that is B-cell deficient but not T-cell deficient.
@BallouxFrancois It just happened that CD8 knockout mice are https://t.co/AAz9fV5p4A “deficient in functional cytotoxic T-cells; however, helper T-cell development and function is comparable to normal.” And are models for both vaccination and challenge trials for LAV vaccines due to specific
@BallouxFrancois Serum B-cell immunity associated with these animals. Combined with evidence of accelerated viral dynamics evident of a non-human host, and the observation that P681H, that is not observed in immunodeficient patient passage but mimics the S1-S2 sequence of MHV, removing a heparan
@BallouxFrancois Sulfate binding motif in the S1-S2, https://t.co/nBCMX6RPGD
Which happened to be a requirement for human infection fitness,
https://t.co/Ytdb1hkZdU
Also suggest a mouse host (which hosts non-Heparan sulfate binding MHV A59 and other non-cell passaged MHV strains) being likely.
@BallouxFrancois https://t.co/k1ViIDUHCq
Notice that for this other case the same kind of deletion—multiple AAs in the S position 144 and no deletion at S position 69-70, and a single deletion in the nsp1 removing a single Methionine residue, was found. This indicate functional B and T cell
@BallouxFrancois Immunity during passage, and the nsp6 SGF and ORF8 are likewise kept intact. The S1-S2 continues to bind Heparan Sulfate in this case, confirming it’s importance for fitness of infection in the human host. In this case the N501Y did not occur.
@BallouxFrancois The persistent infected immunocompromised patient scenario simply don’t fit with the UK isolate’s heightened sensitivity to cytotoxic T cell and evasion of B cell immunity. The GTNGTKR glycan loop being affected also suggest CTLR being different jn the passage host than humans.
@BallouxFrancois @threadreaderapp Unroll

More from Science

"NO LONGER BEST IN THE WORLD"
UNEP's new Human Development Index includes a new (separate) index: Planetary pressures-adjusted HDI (PHDI). News in Norway is that its position drops from #1 to #16 because of this, while Ireland rises from #2 to #1.
Why?

https://t.co/aVraIEzRfh


Check out Norway's 'Domestic Material Consumption'. Fossil fuels are no different here to Ireland's. What's different is this huge 'non-metallic minerals' category.
(Note also the jump in 1998, suggesting data problems.)
https://t.co/5QvzONbqmN


In Norway's case, it looks like the apparent consumption equation (production+imports-exports) for non-metal minerals is dominated by production: extraction of material in Norway.
https://t.co/5QvzONbqmN


And here we see that this production of non-metallic minerals is sand, gravel and crushed rock for construction. So it's about Norway's geology.
https://t.co/y6rqWmFVWc


Norway drops 15 places on the PHDI list not because of its CO₂ emissions (fairly high at 41st highest in the world per capita), but because of its geology, because it shifts a lot of rock whenever it builds anything.

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@franciscodeasis https://t.co/OuQaBRFPu7
Unfortunately the "This work includes the identification of viral sequences in bat samples, and has resulted in the isolation of three bat SARS-related coronaviruses that are now used as reagents to test therapeutics and vaccines." were BEFORE the


chimeric infectious clone grants were there.https://t.co/DAArwFkz6v is in 2017, Rs4231.
https://t.co/UgXygDjYbW is in 2016, RsSHC014 and RsWIV16.
https://t.co/krO69CsJ94 is in 2013, RsWIV1. notice that this is before the beginning of the project

starting in 2016. Also remember that they told about only 3 isolates/live viruses. RsSHC014 is a live infectious clone that is just as alive as those other "Isolates".

P.D. somehow is able to use funds that he have yet recieved yet, and send results and sequences from late 2019 back in time into 2015,2013 and 2016!

https://t.co/4wC7k1Lh54 Ref 3: Why ALL your pangolin samples were PCR negative? to avoid deep sequencing and accidentally reveal Paguma Larvata and Oryctolagus Cuniculus?
1. Project 1742 (EcoHealth/DTRA)
Risks of bat-borne zoonotic diseases in Western Asia

Duration: 24/10/2018-23 /10/2019

Funding: $71,500
@dgaytandzhieva
https://t.co/680CdD8uug


2. Bat Virus Database
Access to the database is limited only to those scientists participating in our ‘Bats and Coronaviruses’ project
Our intention is to eventually open up this database to the larger scientific community
https://t.co/mPn7b9HM48


3. EcoHealth Alliance & DTRA Asking for Trouble
One Health research project focused on characterizing bat diversity, bat coronavirus diversity and the risk of bat-borne zoonotic disease emergence in the region.
https://t.co/u6aUeWBGEN


4. Phelps, Olival, Epstein, Karesh - EcoHealth/DTRA


5, Methods and Expected Outcomes
(Unexpected Outcome = New Coronavirus Pandemic)