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Sharing this story. What a way to kick things off with @PittCVR How does a virus with a proofreading polymerase rapidly evolve? In the case of SARS-CoV-2 we believe that altered antigenicity can arise via deletions in Spike. 1/11 https://twitter.com/10queues/status/1329803761083064321
In a patient with a long-term infection we sequenced viruses with deletions in the NTD. These overlap and match deletions found in other long term infections, suggesting convergent evolution to evade a common pressure. 2/11
Here are the papers.
https://doi.org/10.1016/j.cell.2020.10.049
https://www.nejm.org/doi/full/10.1056/NEJMc2031364 3/11
https://doi.org/10.1016/j.cell.2020.10.049
https://www.nejm.org/doi/full/10.1056/NEJMc2031364 3/11
We identified four sites in the NTD that appear to be enriched for in-frame deletions that are resolved without a stop codon. We term these recurrent deletion regions, RDRs. Other sites like RBD do not tolerate deletions. 4/11
Variants with deletions in spike can spread between humans and form clusters of infected individuals. Sometimes these can lead to smaller minor lineages. At least once, viruses sharing a deletion have become abundant (2.5% of all GISAID sequences in a month) 5/11
We believe one deletion variant has been circulating since mid summer in Europe and has been acquired in mink in Denmark along with other mutations. A wonderful thread by @firefoxx66 https://twitter.com/firefoxx66/status/1324095151984312324 6/11
These sites correspond to two defined antigenic regions. One bound by antibodies 4A8 and 4-8 https://science.sciencemag.org/content/369/6504/650
https://www.nature.com/articles/s41586-020-2571-7 7/11
https://www.nature.com/articles/s41586-020-2571-7 7/11
The second site corresponds to Fabs from patient serum defined by
https://doi.org/10.1016/j.cell.2020.06.025 @cobarnes27 @bjorkmanlab and colleagues 8/11
https://doi.org/10.1016/j.cell.2020.06.025 @cobarnes27 @bjorkmanlab and colleagues 8/11
The first site also corresponds a region where rVSVs bearing the SARS-CoV-2 spike evolved to resist antibodies in donor serum
https://elifesciences.org/articles/61312 from the laboratories of @theodora_nyc @PaulBieniasz 9/11
https://elifesciences.org/articles/61312 from the laboratories of @theodora_nyc @PaulBieniasz 9/11
Given the virus acquires deletions within patients and as it circulates we believe that we should be vigilant in looking for deletions that have the capacity to alter many amino acids at once and the structures they form. 10/11
