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Ryan Hisner Profile picture
@LongDesertTrain
Nov 22 • 3 tweets • 2 min read Twitter logo Read on Twitter
Another lineage seems to have entirely deleted ORF7a, ORF7b, & ORF8
A branch of GE.1.2 (XBB.2.3.10.1.2 = XBB.2.3 + S:N148T, ∆N185, F186I, K478R + ORF1a:G661S, P1921S, V4369A + ORF7a:P99S)
This makes ~5 lineages I've seen w/massive deletions like this. 1/3
github.com/sars-cov-2-var…
This branch has some other interesting aspects. S:A376S represents the 3rd AA residue at that spot. (T-->A-->S).
S:R478T represents the 3rd substitution there. In this case it's come back home to the Wuhan residue after two detours. (T-->K-->R-->T) 2/3 Image
Previous 🧵 on GW.5.1.1, still my favorite XBB lineage. Turns out the double-TRS thing I described is most likely a sequencing artifact that the deletion somehow created. Still waiting on the final verdict of the professional sequencers on this though. 3/3

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More from @LongDesertTrain

Ryan Hisner Profile picture
Nov 24
I spend a lot of time analyzing and documenting outlier SARS-CoV-2 sequences. Recently, I’ve noticed a fascinating pattern: the repeated appearance of paired mutations in two narrow NSP12 regions >2400 nucleotides distant from each other. 1/45
NSP12 is the RNA-dependent RNA polymerase (RdRp), part of the SARS-CoV-2 replication complex, which also includes NSP7-10 and NSP13-14. I discussed some basics of the RdRp & coronavirus genome replication previously. 2/45
The first two-thirds of the SARS-CoV-2 genome consists of ORF1a & ORF1b. When the full genome enters a ribosome, the cell protein-making machine, only ORF1a is translated ~75% of the time. The ribosome hits a stop codon & cuts loose. No ORF1b. 3/45 Image
Read 25 tweets
Ryan Hisner Profile picture
Nov 7
GW.5 is my favorite XBB* lineage. It's always pulling crazy tricks, like deleting entire genes or adding 5-7 AA mutations at once. Here's it's latest antic: grabbing a chunk of the nucleocapsid gene (top) and stuffing it into the spike NTD (bottom). 1/4 Image
These two sequences share two other mutations not found in other related sequences and are from different labs on opposite sides of the world, so this is real, not an artifact. 2/4 Image
Incredibly, this exact insertion, in the exact same location, has occurred once before, and in a completely unrelated sequence—an XBC.1.2.1 from Denmark collected in December 2022. (XBC is a "Deltacron" lineage now mainly circulating in Australia.) 3/4
Read 4 tweets
Ryan Hisner Profile picture
Oct 29
What’s new in the world of SARS-CoV-2 accessory proteins? In this 🧵, I’ll recap their evolution so far & describe a possible new trend: partial or total deletion of ORF7a, ORF7b, & ORF8—particularly in GW.5.1.1, an XBB.1.19 + FLip lineage—plus an ORF9b/N bonus TRS surprise! 1/45
Image
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The SARS-CoV-2 accessory proteins are ORF3a, ORF6, ORF7a, ORF8, ORF9b, and N* (the last absent from Delta). While the non-structural & structural proteins are absolutely essential for replication, accessory proteins are not. 2/45
In cell culture & in mice, deleting each accessory protein (one at a time) causes only slight-to-moderate reductions in viral replication & pathogenesis. ORF3a & ORF6 seem more crucial than ORF7a, ORF7b, and ORF8. (ORF9b & N* are excluded from these studies). 3/45 Image
Read 48 tweets
Ryan Hisner Profile picture
Oct 1
I think this preprint, by @Stuartturville, is potentially one of the more important recent SARS-CoV-2 papers. It promises to unwrap some of the most mystifying aspects of Omicron surrounding cell entry, TMPRSS2 use, & reduced lung invasion/pneumonia. 1/48
When BA.1 emerged, it was apparent it did not cause the same degree of pneumonia or disease severity as Delta (though unprecedented levels of infection resulted in similarly large numbers of hospitalizations & deaths in many areas). h/t @mike_famulare 2/48
Many studies showed this was attributable to Omicron’s impaired ability to infect lung cells & reduced cell-cell fusion (syncytia formation). But what accounted for these attributes of Omicron?
(Image 1 from paper by @GuptaR_lab, @veeslerlab @sigallab @SystemsVirology) 3/48
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Read 48 tweets
Ryan Hisner Profile picture
Sep 28
Charles Chaplin, ultra-influential author and public health official in the early 1900s, said almost the exact same thing. If disease is airborne, people will despair & not be properly sanitary. Therefore, we must tell them disease is not airborne. 1/3
thebaffler.com/salvos/airborn…

Image
Chaplin's view was influential—not because the evidence favored droplet transmission but because his views led to politically acceptable conclusions. With droplet transmission no public action or business regulation was required. @BenEhrenreich: 2/3 thebaffler.com/salvos/airborn…
Image
It's hard to put it any better than @jljcolorado: "Droplets & surfaces are very convenient for people in power—all the responsibility is on the individual. ...if you admit it is airborne, institutions, governments, & companies have to do something." 3/3
(Credit to @mdc_martinus) Image
Read 4 tweets
Ryan Hisner Profile picture
Sep 26
The main database for SARS-CoV-2 genomes—GISAID—has been operating so slowly for the past 4 days that it is essentially non-functional. We know GISAID is actively throttling accounts, possibly through some sort of algorithm.
Is this accidental or intentional? No one knows. 1/4
Every mouse click or any other action results in a 5-20-second delay. Is this necessary because there is some sort of long-lasting technical problem at GISAID? The result of a faulty algorithm? Something else? No one knows. 2/4
Is the network on the verge of collapse? Or is everything operating perfectly & the current uselessness of GISAID just a technical glitch? If the latter, why is it taking so long to fix? When will GISAID be operational again?
Again, no one knows. 3/4
Read 4 tweets

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