Thursday, August 19, 2021

An Interesting Bit Of Cell Biology With Variant Spike Proteins.

SequenceIsJust
TheBeginningVille


Sequencing the nucleotides of genes allows you to determine the coded for sequence of amino acids  in the protein concerned.

As a result, changes in the nucleotides in the gene sequence (i.e. mutations) lead to changes in the amino acids in the protein. Such changes are how the SARS-Cov-2 viral variants are generated.

Once the amino acid sequences are known that structural biologists jump in and try to figure out how changes in variants alter protein topology and, potentially, the way the protein works.

But, even with all this important and elegant 'molecular' work, the next step is to test the function of those mutated/changed/variant proteins in cells.

And a group from Boston has deposited a pre-print wherein they present some interesting data with the various SARS2-Cov-2  S-protein variants.

One of the interesting things these folks did was make funky 'pseudo' viruses that are decorated with the various S protein variants from SARS2-Cov-2. They then looked to see how fast those variants decorated pseudoviruses fuse with cells expressing the ACE2 receptor on their surface.

Here are the data which show that the Delta variant S protein (red line) causes more rapid membrane fusion in their experiments:



This group also did this with cell-cell fusion which led them to make the following conclusion:
...Our findings from both cell-based and pseudovirus-based assays suggest that the Delta variant can infect a target cell substantially more rapidly than the other variants we tested, either by more effective attachment or faster fusion kinetics...

It will be very interesting to see if this finding holds up and if it explains, at least in part, why the Delta variant virus is more infectious in people.



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Again, while I'm a biologist our group does not do research on viruses....We do, however, develop all kinds of assays to test gene/protein variant function in various cell models.




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2 comments:

Booey said...

Very interesting Ross. Isn't the 'viral load' associated with the Delta variant one of the factors in the speed of spread?

RossK said...

Booey--

Yes. Thus, folks have been trying to figure out the mechanism of the increased infectivity. Rapid spike mediated fusion of the virus with upper respiratory tract cells could be a part of that.