- Still more new NSP1 mutations in the BA.3.2 uploaded from the Netherlands today. We've never seen anything like this kind of rapid evolution in NSP1 (whose primary role is to shut down host-protein translation and degrade host mRNA). I've labeled all BA.3.2-specific NSP1 muts here. 1/3
- Another weird aspect of BA.3.2 evolution so far: an extraordinary number of NSP1 mutations. NSP1 is only 180 AA, but a new mutation shows up almost every day there, often on top of previous new ones. The @nextstrain.org visual here can't even accommodate all the NSP1 muts—at least 2 are invisible.
- I suspect these are compensatory mutations for the ∆84-86 and/or ∆141-143 NSP1 deletions. At least one study that found NSP1 deletions from 82-86 to be deleterious, & the lack of 82-86 deletions in nearly all major lineages (despite countless independent acquisitions of them) supports this. 2/3
- And ∆141-143 is definitely deleterious. The phylogenetic evidence for this was already very strong, and two separate studies have confirmed that ∆141-143 reduces viral fitness and NSP1's ability to shut down host translation. 3/3 bsky.app/profile/ryan...
- ORF6:D61L is in all BA.2 & BA.4 (incl XBB & BA.2.86) but not BA.5. NSP1:∆141-143 is more of a BA.4 specialty. A recent preprint confirmed what we'd already suspected: ∆141-143 is harmful It is less able to shut down host translation that NSP1 without ∆141-143. 7/ www.biorxiv.org/content/10.1...
