Being one of the most important studies we have read, we will take the time to explain all the concepts, one by one.
2) ๐๐๐๐ฉ ๐๐ง๐ ๐ผ๐ช๐ฉ๐ค๐ฅ๐๐๐๐ค๐จ๐ค๐ข๐๐จ ?
Autophagosomes are double-membrane vesicles formed during autophagy, that sequester cytoplasmic cargo like proteins, organelles and pathogens targeted for degradation.
Upon SARS-CoV-2 invasion, host cells induce autophagy ...
3) ...as an intrinsic antiviral defense mechanism. Autophagosomes capture invading viral particles and components.
Cargo-loaded autophagosomes then fuse with lysosomes. This degrades intact virions and disrupts infection.
4) ๐๐๐๐ฉ ๐๐ง๐ ๐๐ฎ๐จ๐ค๐จ๐ค๐ข๐๐จ ?
Lysosomes are membrane-bound organelles that contain digestive enzymes and maintain an acidic pH optimal for degradation. As part of the autophagy response, SARS-CoV-2 virions and viral components that are sequestered inside autophagosomes
5) ...are delivered to lysosomes upon fusion.
The acidic pH and hydrolases inside lysosomes promote destruction of viral structural proteins, genetic material, lipids etc. This degrades and destroys intact virions.
6) ๐๐๐๐ฉ ๐๐จ ๐๐ฎ๐จ๐ค๐จ๐ค๐ข๐๐ก ๐๐๐๐ง๐๐๐๐ฉ๐๐ค๐ฃ ๐ค๐ ๐๐ผ๐๐-๐พ๐ค๐-2 ?
It refers to the process by which the virus is targeted to lysosomes and broken down through the cell's lysosomal machinery.
And finally, ๐ผ๐ช๐ฉ๐ค๐ฅ๐๐๐๐ฎ ๐๐ฃ๐๐ช๐๐ฉ๐๐ค๐ฃ refers to ...
7) ... the activation of this autophagy process in response to the infection caused by the SARS-CoV-2 virus.
After this short presentation, we can now present this study
8) The Omicron variant of SARS-CoV-2 is more resistant to autophagy induction compared to early 2020 SARS-CoV-2 strains and the Delta variant. Activation of autophagy reduced replication of early strains and Delta more strongly.
9) Mutation T9I in the SARS-CoV-2 envelope (E) protein conferred increased autophagy resistance to Omicron variants compared to strains without this mutation.
10) E mutation T9I leads to increased accumulation of autophagosomes by more strongly inhibiting autophagic flux. It interacts more with components of the autophagosome assembly machinery.
11) Viral particles containing E T9I were less sensitive to autophagy induction upon entry compared to particles with E T9. However, E T9I did not alter particle assembly or infectivity.
12) Rare Omicron isolates retaining the ancestral E T9 were more sensitive to autophagy induction compared to E T9I isolates. Recombinant early SARS-CoV-2 gained autophagy resistance by acquiring E T9I.
13) In summary, the study identifies E T9I as a mutation that allows Omicron to escape autophagy, which may have contributed to its emergence and spread by evading this innate immune defense. Acquiring resistance to autophagy is an evolutionary adaptation of SARS-CoV-2.
In several threads, we indicated that this E:T9I mutation by reducing the pathogenicity of Omicrons had changed the face of the pandemic.
There was a sort of trade-off among the Omicrons ...
15) ... less pathogenic but more infectious with better immune escape thanks to Spike mutations.
Omicron was therefore more dangerous, which is the case for a more infectious and less pathogenic virus.
16) As we discovered that E:T9I may have contributed to the emergence and spread of Omicrons by evading the innate immune defense, it is really a key evolutionary adaptation of SARS-CoV-2.
Thanks for reading ๐
H/t @DavidJoffe64 @siamosolocani @C_A_G0101
@mrmickme @DrInfoSec
โข โข โข
Missing some Tweet in this thread? You can try to
force a refresh
"Zoonotic infections are not limited to rural environments and commercial poultry operations but extends into the heart of our urban centers" biorxiv.org/content/10.110โฆ
2) Highly pathogenic avian influenza H5N1 viruses of clade 2.3.4.4b arrived in North America in late 2021/early 2022 and have since spread widely, infecting both wild and domestic birds.
3) Surveillance was conducted in New York City from January 2022 to November 2023 to detect H5N1 viruses in urban wild birds. 1927 samples were collected from 895 birds representing 80 species.
2) In this study, they experimentally evolved the SARS-CoV-2 spike protein by passaging a recombinant vesicular stomatitis virus (VSV) bearing the spike in 4 different human cell lines expressing different levels of host entry factors like ACE2 and TMPRSS2.
3) After 20 passages, they identified 16 spike mutations that were fixed across the cell lines. Some of these mutations like H655Y and Q493R have also emerged in globally circulating variants.
2) Mitochondrial dysfunction has emerged as a prominent factor contributing to the diverse and persistent symptoms observed in patients with long COVID syndrome. Impaired mitochondrial function could underlie symptoms like chronic fatigue, cognitive issues ...
3) ...and muscle weakness through mechanisms like reduced energy production and increased oxidative stress.
Evidence of mitochondrial dysfunction in long COVID comes from studies showing abnormalities in mitochondrial respiration, gene expression, and ...
2) The study investigated viral persistence and its association with long COVID symptoms in 225 patients who recovered from mild COVID-19 in China. Tissue and blood samples were collected at 1, 2, and 4 months post-infection.
3) SARS-CoV-2 RNA was detected in various solid tissues like lung, liver, kidney, stomach, intestine, brain, up to 4 months post-infection, though detection rates gradually decreased over time.
Viral RNA was also found in blood components of immunocompromised patients ...
2) Innate immunity was long overlooked compared to adaptive immunity, but over the past 50 years research has revealed it to be a highly sophisticated and interconnected system.
3) Major discoveries include pathogen recognition receptors (PRRs) like Toll-like receptors (TLRs) and Nod-like receptors (NLRs), which detect pathogens and damage. This links innate and adaptive immunity.