Thread by @PeacockFlu

We think we can see some evidence of circulating SARS-CoV-2 isolates which have picked up short sequences of human mRNAs and inserted them into thier genomes so we wrote a virological post about it.

virological.org/t/putative-hos…

While substitutions and deletions are common and well described for SARS2, insertions are rarer, though several widespread lineages have unique insertions. Mu/B.1.621, A.2.5, B.1.214.2, and AT.1 all have insertions in Spike

We looked at where insertions cluster in Spike and found they mostly fall in the NTD or near the S1/S2 site. This is very similar to where deletions are found.

When you look at where these RNA insertions might come from, many show homology to the viral genome itself, either locally or distally. For example the insertion from AT.1 shows homology to the SARS2 3'UTR implying copy-choice recombination.

More interestingly, for those that dont show homology to the viral genome, a subset show high levels of homology to human transcripts.

Though the evidence is weaker, this is somewhat the case for the variant Mu/B.1.621.

This shouldnt come as a big suprise as several RNA viruses are thought to have incorporated host RNA sequences into thier genomes. This includes Coronaviruses, Flaviviruses and Influenza (which has probably incorporated host RNA to create a furin cleavage site at least once)

To conclude, insertions can probably act as wildcard mutations, allowing the virus to rapidly change phenotype (for example via the furin cleavage site insertion in SARS2). We are now performing phenotypic assays to characterise some of these insertions.

Many thanks to @wendybarclay11, @DavidLVBauer, @influenzal, Ada and others from the UK G2P and COG-UK for thier help on this report!

Flaviviridae even, whoops!