Pinned
Stuart Turville
1,641 posts
Stuart Turville
@StuartTurville
Associate Professor in Virology
Sydney, New South Wales
Joined August 2019
Images of SARS-CoV-2 cultures often tell us a thousand words. Here we have the Omicron lineage XBB.1.5 growing in two engineered cells. Both equally express ACE2 and TMPRSS2. Visually this sums up our journey into the complicated entry pathway of Omicron lineages......1/
- Evolutionary trajectory of SARS CoV-2 from Ancestral Clade A to JN.1. What does the below mean? The virus is consolidating towards a specific pool of ACE2. Early on the ACE2 pool the virus favoured needed to be cut/cleaved. Now it heavily favours (well for JN.1) uncleave ACE2.
- Replying to @Mike_Honey_ and @EricTopolBA5 has switched tropism again to use TMPRSS2. It’s like a viral yo-yo. Here’s what Delta, BA1 and BA5 look like in cells with TMPRSS2 when exposed to positives samples and left for three days.
- In 2021 we made tools to rapidly capture & analyse live SARS CoV2 variants. To rank them for evasion to antibodies we used antibodies pooled from thousands of convalescent/ vaccinated donors. In late November we isolated the first Omicron case in a Australia. Here is its rank
- Replying to @umm_rit_BA5 isn’t quite Delta yet but is on its way (sits in between Delta and BA2 in its ability to engage the Ace2-TMPRSS2 pathway). A p681r change would be very interesting to see if it can “yo yo” fully from BA2 to the tropism of Delta again.
00:00 - Replying to @SwaledaleMutton @Mike_Honey_ and @EricTopolThis is what we use to characterise emerging variants. nature.com/articles/s4156… In brief BA1 uses TMPRSS2 poorly, BA2 even more so. BA5 has now switched. A lot of this work we do in real time as the samples build in the community.
- 1- In 2021 we built a simple/powerful platform to rapidly isolate/test SARS-CoV-2 variants. The full recipe we submitted for review late last year: researchsquare.com/article/rs-121… Its power is speed/simplicity. Overnight the virus does its work by literally melting the cells together.
00:00 - Replying to @StuartTurville2/ To cut a long story very short, the difference in the two cell types and why one looks like a Delta infection (but is XBB.1.5) is the pool of ACE2 that is present in the cell with obvious replication revealed by cell-cell fusion. This pool of ACE2 is resistant TMPRSS2 action
- Replying to @StuartTurville11/ To really get our heads scratching. Here is the pre-print that maps the biology of this. Stefan Pohlmann's work in 2014 on SARS CoV-1 was key here!
- Replying to @nytimes and @CosmosMagazineHere is another example. It is effectively any culture that replicates the virus at high levels.
00:00 - Replying to @StuartTurville3/ Beautiful work by Stefan Polhmann's team in 2014 on SARS CoV-1 lead us to look at the dynamics between ACE2 and TMPRSS2 on SARS CoV-2 entry.
- Replying to @StuartTurville5/ Whilst early SARS CoV-2 entered in a manner like SARS CoV-1... TMPRSS2 cleaved ACE2 facilitated entry only for SARS CoV-2 that was prior to Omicron. What defined Omicron entry, was progressive attenuation in settings where ACE2 was cleaved by TMPRSS2. It was a off switch....
- medrxiv.org/content/10.110… Our snapshot of clinically isolated BA5 virus: 1- Antibodies derived from thousands of donors observes all Omicron variants (esp. BA1, BA2 & BA5) are evasive. 2- Potency of Evusheld and Sotrovimab reduced. 3- Tropism shift back to using TMPRSS2
