Slack / Private Message Drop — page 386

[2021-01-11 16:19:33] [Robert Garry] The NSP6 deletion is downstream of a crazy T rich region. [2021-01-12 05:06:35] [Robert Garry] One thing to consider about SC2 is that in some patients we see extremely low Ct values - 8-9 not that unusual. That converts to 2 logs higher virus load than we see with Ebola, Lassa etc. Couple that with the not well-characterized editing/proofreading functions, tendency to generate short deletions seen with MHV and others, etc and the you maybe - just maybe - start to see why a mechanism of progression of individual mutations might not be the only pathway for evolution of CoVs. [2021-01-12 05:17:34] [Robert Garry] https://jvi.asm.org/content/jvi/71/4/2959.full.pdf [2021-01-12 05:20:22] [Kristian Andersen] That's pretty interesting - same signature [2021-01-12 05:22:42] [Robert Garry] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC191424/ [2021-01-12 05:26:50] [Robert Garry] also interesting [shared file(s): image.png] [2021-01-12 05:38:42] [Robert Garry] I have to give a lecture at 8;30 but there is more gold to mine down this shaft... [2021-01-12 07:31:02] [Kristian Andersen] If we weigh being 'successful' in a population due to inherently being (a) inherently more transmissible vs (b) being able to escape immunity, an important consideration is what the immune selection pressure is. Is it the one experienced within a single (chronically) infected individual or is it standing immunity as a virus is spreading through a population? Given that we're seeing the same sets of mutations in independent lineages in different areas, clearly there must be a strong and directed selection pressure (immune or otherwise). I'm starting to think that it's probably the former - rare events happening in individual people (or a zoonotic host - probably not likely, but has to be considered) that may or may not be immunocompromised and may and may not have received treatments. The increased transmission effects (probably high for UK lineage) and population immune evasion (probably higher in RSA/Brazil lineages) are just side-effects of the intrahost selection pressures that fixed the mutations in the first place - I don't necessarily think they _are_ the selection pressures. The transmission phenotype may be a side-effect of "better binding" and population immune evasion a side-effect of intrahost immune evasion. The reason why we're (a) observing these now, and (b) they pop up in areas of high previous attack rates, might be more down to chance than selection. Chronic infections are probably rare events, take time to fix a large number of (onwards successfully) mutations, and therefore more likely to pop up in areas of high previous attack rates. If they're then able to escape _some_ immunity in the population, they're also more likely to successfully propagate in such a population. [2021-01-12 12:04:47] [Kristian Andersen]