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Slack / Private Message Drop, p.24 [SLACK_000238] · slack_pm:msg:00238

Date: 2020-05-13 04:36
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry

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Couple of points. First, in the human sequencing most if not all of the seq are from nasal swabs taken at diagnosis,ie. near peak virus load. It might be interesting to look later in disease when Ct values have increased - that's where the variants if they exist will be found in vivo. Monkey studies can get to these late variants too if they exist and ourprimate center is sending samples to KGA. Def a bottleneck in human transmission of virus variants - there is awhole literature on this in HIV. Persistent HIV infection accumulates variants - usually only one or a few variants transmitted - macrophage tropic vs T-cell tropic viruses are selected for. Second, there are a lot of ways to dopassage in cell culture. Here's an 40 year old paper I did in graduate school with CC King who - lets say had somechallenges in gs but went on to be Taiwan's "greatest" virologisthttps://www.sciencedirect.com/science/article/abs/pii/0042682279901867?via%3Dihub Undiluted, diluted passage -different cells - incubation time generate different levels of DI particles (big deletions) substitutions etc. Would have been great to have a sequencer then - excuse me while I get in my time machine and go back to retrieve a few samples.

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journal https://www.sciencedirect.com/science/article/abs/pii/0042682279901867?via%3Dihub

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2020-05-13 04:36 Robert F. Garry

Couple of points. First, in the human sequencing most if not all of the seq are from nasal swabs taken at diagnosis,ie. near peak virus load. It might be interesting to look later in disease when Ct values have increased - that's where the variants if they exist will be found in vivo. Monkey studies can get to these late variants too if they exist and ourprimate center is sending samples to KGA. Def a bottleneck in human transmission of virus variants - there is awhole literature on this in HIV. Persistent HIV infection accumulates variants - usually only one or a few variants transmitted - macrophage tropic vs T-cell tropic viruses are selected for. Second, there are a lot of ways to dopassage in cell culture. Here's an 40 year old paper I did in graduate school with CC King who - lets say had somechallenges in gs but went on to be Taiwan's "greatest" virologisthttps://www.sciencedirect.com/science/article/abs/pii/0042682279901867?via%3Dihub Undiluted, diluted passage -different cells - incubation time generate different levels of DI particles (big deletions) substitutions etc. Would have been great to have a sequencer then - excuse me while I get in my time machine and go back to retrieve a few samples.
2020-05-13 04:47 Robert F. Garry open

"My first look at the virus suggested that the pattern of distribution of sequence variation across the genome looked natural, but that may too broad brush." ProfBill has a new long read on Virological on this topic - synonymous mutations look very normal from bat to pangolin.

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