Early #SARSCoV2 from sequences Dec-2019 and Jan-2020 are all closely related as expected in new outbreak. But there is some genetic variation. One classification system (proposed by @arambaut et al) divides early #SARSCoV2 sequences into lineages A and B (nature.com/articles/s4156…)
Lineage A is closer to bat coronaviruses, and so is probably more similar to first virus that entered humans. Lineage B has two mutations that make it more different from bat coronaviruses (T8782C & C28144T), and so probably descends from lineage A. As paper above says:
The Huanan Seafood Market super-spreading event involved lineage B, which went on to dominate globally. Below are trees from academic.oup.com/mbe/advance-ar… showing relationship of lineage B (large circle at bottom) & lineage A (all other circles) for two plausible outgroup rootings:
Anyway, so far the mutations that distinguish lineage A and B have just been genetic markers useful for tracing virus's evolution and classifying sequences into different lineages. But the new pre-print (biorxiv.org/content/10.110…) mentioned at top of this thread changes that.
Specifically, this pre-print looks at the functional effect of the amino-acid change caused by nucleotide mutation C28144T, which recall is one of the two mutations that makes lineage B more different from bat coronaviruses than lineage A.
That mutation changes residue 84 in the ORF8 protein from Ser to Leu. Pre-print shows secreted ORF8 modulates ability of macrophages to secrete cytokines. And the two different variants at residue 84 lead to different changes in secretion of cytokines such as IL-6, IL-8, and MIF.
These results imply the C28144T nucleotide mutation (Ser84->Leu ORF8 amino-acid mutation) could subtly alter immune response to infection. Because relationship between cytokine expression and overall infection/disease is complex...
... it's not possible to say if or how the mutation might impact either viral transmission or disease severity. But the results do suggest that we should consider the possibility that this early lineage-defining mutation has a functional effect.
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This is a really good and thoughtful thread by @stuartjdneil! It's great to see these clear explanations and chains of reasoning that more and more virologists are posting about the topic of risk-benefit of certain experiments. (1/3)
Hi @angie_rasmussen, thanks for asking these important questions about risk / benefits of different types of virology experiments. Because you locked your Tweet thread, I can't reply, so will post my thoughts here in a new thread that anyone can reply to. 🧵
This is not about being pro- or anti-chimeric virus, but about risks of specific experiments. As scientists we have this responsibility. My favorite essay is Feynman's The Value of Science (calteches.library.caltech.edu/40/2/Science.p…), which he wrote after his field of physics built nuclear bomb.
As we all know, experiments that manipulate viruses have yielded important scientific insights & been of tremendous value to human health. This includes smallpox vaccine, oncolytic viruses, gene delivery, etc. Even some vaccines (eg, J&J #SARSCoV2 vaccine) are chimeric viruses!
@zeynep, here are some more interesting early #SARSCov2 dates for you. Check out the description of the samples in the final published version of this paper (academic.oup.com/cid/article/71…): "Eight COVID-19 pneumonia samples were collected from hospitals in Wuhan in January 2020." (1/3)
See if you can spot difference in how same samples are described in PubMed Central version (ncbi.nlm.nih.gov/pmc/articles/P…), which would have been built from original peer-reviewed manuscript: "Eight COVID-19 were collected from hospitals in Wuhan from December 18 to 29, 2019." (2/3)
Journal early access version of manuscript, which would have been the peer-reviewed version, also says samples from December 18-29, 2019 (web.archive.org/web/2020030800…). There is no correction in journal, so presumably dates changed at post-peer review manuscript proofing stage. (3/3)
Check out @tylernstarr's summary of our new pre-print showing that ACE2 binding is an ancestral and evolvable trait of sarbecoviruses (SARS-related coronaviruses):
Specifically, @tylernstarr used high-throughput binding assays to measure how well receptor-binding domains from nearly all known sarbecoviruses can bind ACE2 from various relevant species:
I have posted an updated version of my pre-print describing #SARSCoV2 sequences from the early Wuhan epidemic that were deleted from the Sequence Read Archive. This revision should clarify some key questions people asked about the original version: biorxiv.org/content/10.110… (1/n)
First, I would like to thank @stgoldst who provided a set of good-faith scientific critiques that he posted as @biorxivpreprint comments on the original version: disq.us/p/2hwabcu (2/n)
My revisions address @stgoldst's comments as well as others posted on @biorxivpreprint or e-mailed to me directly. You can read my detailed response to the comments and description of the revisions here (disq.us/p/2hwapg6). In this thread, I summarize key changes. (3/n)
I am getting lots of questions if my pre-print about some #SARSCoV2 sequences that were removed from Sequence Read Archive tell us anything about lab accident versus natural zoonosis.
I posted summary of pre-print below, but did not directly address this point explicitly (1/n)
The answer is NO. The people using it to strongly support either argument are those that have become so emotionally invested in their opinion that they have lost the ability to analyze anything objectively outside of the framework of that argument. (2/n)
What the pre-print does imply is as follows:
First, there may be additional relevant data in obscure locations that aren't the places where we are accustomed to looking (e.g., on the Google Cloud, in table 1 of a paper on diagnostics, etc):