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Slack / Private Message Drop, p.1013 [SLACK_001227] · slack_pm:msg:10578

Date: 2021-10-03 07:04
Type: chat message · slack
mentioned: Andrew Rambaut
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Vaccines

Recipients on this medium are inferred from channel membership, not per-message addressing.

@Andrew Rambaut !channel yeah - most definitely the template switching or copy-choice error has to involved reading a template 3' to 5'. All you said was true if the template for the jump is a stray mRNA it would need to bereverse complement for going from the neg strand on the replicative intermediate (often visualized asdouble-stranded) to the pos strand (second round). So as you say the first round (pos to neg for the jump) would generate positive RNA that would encode the modified spikes. Not so sure that there is a huge advantage one wayor the other in terms of whether the jump occurs first or second round, There are dozens of rounds of replication both positive to negative (generates replicative intermediates) AND negative to positive which generate mRNAS and genomes.

Extracted statements

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Statement	Grade	Attribution	Stance
All you said was true if the template for the jump is a stray mRNA it would need to bereverse complement for going from the neg strand on the replicative intermediate (often visualized asdouble-stranded) to the pos strand (second round).	own voice, substantive	speaker_own	asserts
Not so sure that there is a huge advantage one wayor the other in terms of whether the jump occurs first or second round, There are dozens of rounds of replication both positive to negative (generates replicative intermediates) AND negative to positive which generate mRNAS and genomes.	own voice, substantive	speaker_own	asserts

Statement

Grade

Attribution

Stance

All you said was true if the template for the jump is a stray mRNA it would need to bereverse complement for going from the neg strand on the replicative intermediate (often visualized asdouble-stranded) to the pos strand (second round).

own voice, substantive

speaker_own

asserts

Not so sure that there is a huge advantage one wayor the other in terms of whether the jump occurs first or second round, There are dozens of rounds of replication both positive to negative (generates replicative intermediates) AND negative to positive which generate mRNAS and genomes.

own voice, substantive

speaker_own

asserts

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

2021-10-03 07:04 Robert F. Garry

@Andrew Rambaut !channel yeah - most definitely the template switching or copy-choice error has to involved reading a template 3' to 5'. All you said was true if the template for the jump is a stray mRNA it would need to bereverse complement for going from the neg strand on the replicative intermediate (often visualized asdouble-stranded) to the pos strand (second round). So as you say the first round (pos to neg for the jump) would generate positive RNA that would encode the modified spikes. Not so sure that there is a huge advantage one wayor the other in terms of whether the jump occurs first or second round, There are dozens of rounds of replication both positive to negative (generates replicative intermediates) AND negative to positive which generate mRNAS and genomes.
2021-10-03 07:05 Robert F. Garry open

If the template is a related pos RNA virus rather than a mRNA in the same cell then you will have a lot of negativestrands. so the question of when the jump happens pos to neg or neg to pos is not an issue.
2021-10-03 07:12 Robert F. Garry open

Finally, Mike Worobey pinged me with a different but related question. He wants to do a virological post (and askedme - old school- to help). His hypothesis is that if there is a co-infection with BANAL-20-52 (NSRS at S1/S2) and oneof the RmYN02 like viruses such as BANAL-20-116 (NSPAAR) you could generate by a template switch orcopy-choice error a virus with something very close to NSPRRARS. It's very possible.
2021-10-03 07:29 Robert F. Garry open

So Yuri - the masterblaster - got that part right about the reverse complement (his pango mRNA is the reverse complement), That being said - I am a little biased toward most of the copy choice errors involving mixed virus infections for the reason that the replication machinery for the virus is complicated by the fact that you need thenucleocapsid proteins and other factors bound to the template to get efficient replication "transcription" ( the pos toneg first round or if you a re a neg strand virus the first neg to pos round). Does not mean it can't involve a mRNA -Yuri even found some examples in the literature - just means for me it's much more infrequent.
2021-10-03 07:46 Robert F. Garry open

https://journals.asm.org/doi/10.1128/JVI.79.11.6620-6630.2005

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