XBB.1.41.1 (S:335S,403K,478R) sublineage with Orf1a:P1220L and N:H300Y growing internationally (251, > 7% in Louisaina in September)

[FedeGueli]

Thanks to a question from Marc Johnson if there wer some sublineage with N2 gene test failure i found this one, maybe it is not related with the question but for sure it is expanding in US and Uk during last month.

Defining mutations: XBB.1.41.1(S:335S,403K,478R) >> C364T > Orf1a:P1220L (C3924T = NSP3_P402L), C18555T > N:H300Y (C29171T)

Gisaid query: ,C3924T,C18555T,C364T

Samples 35 From Usa(Alabama) , UK , Ireland, Israel , Australia

IDs

EPI_ISL_17974948, EPI_ISL_17989726, EPI_ISL_18012574, EPI_ISL_18036936, EPI_ISL_18053693, EPI_ISL_18053723, EPI_ISL_18053726-18053727, EPI_ISL_18053733, EPI_ISL_18053740, EPI_ISL_18053746, EPI_ISL_18053756, EPI_ISL_18053758, EPI_ISL_18053760, EPI_ISL_18056768, EPI_ISL_18057661, EPI_ISL_18060387, EPI_ISL_18060397, EPI_ISL_18065807, EPI_ISL_18072072-18072073, EPI_ISL_18072081, EPI_ISL_18072093, EPI_ISL_18092135, EPI_ISL_18095045, EPI_ISL_18097938, EPI_ISL_18097940, EPI_ISL_18097942, EPI_ISL_18097944, EPI_ISL_18097953, EPI_ISL_18097964, EPI_ISL_18099263, EPI_ISL_18104449, EPI_ISL_18107756, EPI_ISL_18108106,

First: hCoV-19/England/CLIMB-CM7YGDNA/2023 | Original | EPI_ISL_17974948 | 2023-06-25 Last: hCoV-19/USA/NY-NYULH-15770/2023 | Original | EPI_ISL_18095045 | 2023-08-06

Tree: https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_35258_e2a400.json?c=gt-N_300&label=id:node_7003861

[FedeGueli]

This is flying in Louisiana ( 10% there both in last two weeks of July and the first two of August) ping @corneliusroemer consider that N:300 could have an impact on N gene testing.

[FedeGueli]

@corneliusroemer i was looking at epi in Louisiana it seems quite fastly growing with this lineage at 10% but XBB.1.41 there. And with XBB.1.41.2 they together reach around 17-18% in August (over 100 samples) while S:F456L seems still far at less than 7-8% https://twitter.com/BNOFeed/status/1694484633365189061 also hospitalization are announced to be on the rise by CDC (Texas,Georgia, Tennessee too) : https://twitter.com/Laurie_Garrett/status/1694372598073676219

I suggest to designate this one too also for the possible N-GTF due to N:300 mutated.

[FedeGueli]

new samples Wi, NY

[FedeGueli]

67 tot. Many international samples beyond US.

[FedeGueli]

68 prevalence in Louisiana seems less than before but anyway around 10%

[xz-keg]

Sorry it is JC.5. I commented in a wrong place

[Over-There-Is]

Designated JW.1

JC.5

[FedeGueli]

Designated JC.5 via https://github.com/cov-lineages/pango-designation/commit/d3d7c0998d613c9a35c5746cd03bb6476c492f40

[ryhisner]

Fede, this lineage has a large deletion in ORF7a. Most sequences just appear to lack coverage there, but a few seem to register the deletion correctly—∆27523-27695. It causes a frameshift that completely changes the last 20 AA of ORF7a and which also leads to fusion with ORF7b. Furthermore, most of the recent sequences from England also have the new ORF7b—∆27791-27792.

So this results in a brand new protein with the first 44 AA from ORF7a, the next 20 from a new reading frame in ORF7a, and the last 32 from the new ORF7b, the last 17 residues of which are totally different from normal ORF7b.

On top of all that, all the sequences with the new ORF7b also have a 23-nt deletion that erases the ORF8 TRS (∆27887-27909). Damn.

I may have made a mistake somewhere, but I believe the new AA sequence for this modified ORF7a-ORF7b protein would be this:

Residues 45-64 are the brand new ones resulting from the new reference frame at the end of ORF7a. Residues 65-77 are the normal first 13 in ORF7b, and 78-95 are the new ORF7b residues that result from the frameshift caused by ∆27791-27792.

[FedeGueli]

Thank you @ryhisner ! great spot! i noticed that JC.5.1 did a noticeable comeback in collection 42 just yesterday evening, i left this tab open on my pc when falling asleep and this morning i found your comment! This is something to watch closely, in my view. Do you think all the JC.5.1 sequences have the Orf7a deletion? but likely not everyone has the new orf7b right? I ve identified a possible subbranch with the query: C9565T, C11758T, C12325T that similarly fast as Jn.1 baseline: https://cov-spectrum.org/explore/World/AllSamples/Past2M/variants?nextcladePangoLineage=JN.1*&nucMutations1=C9565T%2CC11758T%2CC12325T&analysisMode=CompareToBaseline& obviously it could be biased by N factors so to take it with a big grain of salt.

[FedeGueli]

@ryhisner i have just opened a dedicated issue from your comment: #1328

Please go on the discussion there