XBB.2.3.11 sublineage with M:A104V, ORF1a:A181T, ORF3a:G172C, G14268A, and C25701T first detected in France (106 GISAID seqs as of 2023-08-22; Europe, North America, Asia)

[alurqu]

There may be a XBB.2.3.11 sublineage with M:A104V (C26833T), ORF1a:A181T (G806A; NSP2:A1T), ORF3a:G172C (G25906T), G14268A, and C25701T first detected in France. This lineage also appears to have a G->C nucleotide mutation just after the 28362-28370 deletion in ORF9 which may impact ORF9b:V30.

There may be cause to consider designation of one or more intermediate lineages between the parent XBB.2.3.11 lineage and the lineage proposed here.

As of 2023-08-22, Cov-Spectrum reports 60 good-quality (69 total) XBB.2.3.11+M:104V+ORF1a:181T+ORF3a:172C+14268A+25701T sequences. Source: https://cov-spectrum.org/explore/World/AllSamples/AllTimes/variants?variantQuery=nextcladePangoLineage%3AXBB.2.3.11+%26+M%3AA104V+%26+ORF1a%3AA181T+%26+ORF3a%3AG172C+%26+G14268A+%26+C25701T&nextcladeQcOverallScoreTo=29&

There is too little data to reliably determine the growth rate of this lineage in the country (France) where it is most common, but this lineage may be growing fairly rapidly. It has been detected in 12 countries on 3 continents, and as of 2023-08-22 there are significantly more sequences in GISAID than in CoV-Spectrum where data was last updated on 2023-08-19. Possible impacts of non-synonymous mutations on viral relative fitness are discussed below.

As of 2023-08-22, UShER shows all of the CoV-Spectrum samples are on a single subtree with evidence of additional branching:

To visualize on UShER: https://nextstrain.org/fetch/github.com/alurqu/pango-designation-support-alurqu/raw/main/2023/08/subtreeAuspice1_genome_CoV-Spectrum_XBB.2.3.11%2BM_104V%2BORF1a_181T%2BORF3a_172C%2B14286A%2B25701T.json?c=gt-ORF3a_172&label=id%3Anode_7356980

GISAID query: C26833T, G806A, G25906T, G14268A, C25701T

First GISAID sequence: Ile-de-France, France 2023-05-22

Most Recent GISAID sequence: Ontario, Canada 2023-08-14

A zip archive of GenBank-formatted and derived metadata and FASTA files plus CoV-Spectrum-derived UShER output files for these sequences is available at Support-XBB.2.3.11+M_104V+ORF1a_181T+ORF3a_172C+14286A+25701T.zip

A CoV-Spectrum list of GISAID EPI ISLs for good-quality sequences is available at gisaid-epi-isl-XBB.2.3.11+M_104V+ORF1a_181T+ORF3a_172C+14268A+25701T.txt

Potential effects of the non-synonymous mutations on viral relative fitness

Now to consider the clade-specific Bloom and Neher estimates (from https://github.com/jbloomlab/SARS2-mut-fitness/blob/main/results/aa_fitness/aamut_fitness_by_clade.csv) of the fitness effects of the non-synonymous mutations in their order on the UShER tree:

For M:A104V,

clade,gene,aa_mutation,delta_fitness 20A,M,A104V,-1.3216 20B,M,A104V,0.096687 20C,M,A104V,-0.75338 20E,M,A104V,-0.1322 20G,M,A104V,-0.31455 20I,M,A104V,0.075529 21C,M,A104V,-0.16369 21I,M,A104V,-1.5489 21J,M,A104V,-1.5756 21K,M,A104V,-0.012062 21L,M,A104V,-0.034943 22A,M,A104V,0.1043 22B,M,A104V,-0.0039761 22C,M,A104V,0.0066427 22D,M,A104V,0.13321 22E,M,A104V,-0.45698 22F,M,A104V,0.51454 23A,M,A104V,0.59722

M:A104V exhibits sign epistatis between clades with a positive delta_fitness in the XBB clades for which data is available 22F and 23A.

For ORF1a:A181T (NSP2:A1T),

clade,gene,aa_mutation,delta_fitness 20A,ORF1ab,A181T,0.4541 20B,ORF1ab,A181T,-0.12603 20C,ORF1ab,A181T,0.69026 20E,ORF1ab,A181T,-1.4323 20G,ORF1ab,A181T,-0.71803 20I,ORF1ab,A181T,0.64 21C,ORF1ab,A181T,-0.048028 21I,ORF1ab,A181T,0.075645 21J,ORF1ab,A181T,0.20418 21K,ORF1ab,A181T,0.74246 21L,ORF1ab,A181T,0.70443 22A,ORF1ab,A181T,-0.27274 22B,ORF1ab,A181T,0.29769 22C,ORF1ab,A181T,0.30749 22D,ORF1ab,A181T,0.92246 22E,ORF1ab,A181T,-0.34493 22F,ORF1ab,A181T,-0.30134 23A,ORF1ab,A181T,0.11896

ORF1a:A181T also exhibits sign epistatus between clades with weakly mixed delta_fitness in the XBB clades 22F and 23A.

For ORF3a:G172C,

clade,gene,aa_mutation,delta_fitness 20A,ORF3a,G172C,0.87255 20B,ORF3a,G172C,1.3092 20C,ORF3a,G172C,0.99406 20E,ORF3a,G172C,0.58623 20I,ORF3a,G172C,1.1417 21C,ORF3a,G172C,1.007 21I,ORF3a,G172C,0.53968 21J,ORF3a,G172C,1.0177 21K,ORF3a,G172C,1.3135 21L,ORF3a,G172C,0.67395 22A,ORF3a,G172C,0.94976 22B,ORF3a,G172C,0.88703 22C,ORF3a,G172C,-0.30292 22D,ORF3a,G172C,0.51675 22E,ORF3a,G172C,0.50294 22F,ORF3a,G172C,1.5038 23A,ORF3a,G172C,0.36773

ORF3a:G172C provides positive delta_fitness to varying degrees, except in Clade 22C (BA.2.12.1) including a decently strong positive delta_fitness in Clade 22F (parental XBB).

Considering the fitness effects of the non-synonymous mutations, this lineage could plausibly have a growth advantage especially if the advantage from ORF3a:G172C holds in the not-yet-measured Clade 23E (XBB.2.3).

[FedeGueli]

ahaha mind transmission finally proven (kidding) i have this one open on my scree this morning ( i will propose a couple more!)

[alurqu]

It may be just an oddity, but I just realized that all of the (first 9) BA.2.86 sequences have M:A104V.

Until recently, the only lineage with M:A104V at >= 50% prevalence appears to have been BQ.1.32.

[FedeGueli]

GS.4 via https://github.com/cov-lineages/pango-designation/commit/3760d6c5452a7ac689732c489f8a8ccd1c189b0b

[alurqu]

ORF3a:G172C to a sublineage with S:N185D also designated as GS.4.1. I would have made a designation node at https://github.com/cov-lineages/pango-designation/commit/5dde128ae6d61a3b6f10277dc227f63906f7a7e3 due to the branching from that point, but oh well.

[FedeGueli]

ORF3a:G172C to a sublineage with S:N185D also designated as GS.4.1. I would have made a designation node at cov-lineages/pango-designation@5dde128 due to the branching from that point, but oh well.

I'll add that milestone too.

[MCB6]

It appears to have reached domination in Ukraine.

[FedeGueli]

It appears to have reached domination in Ukraine.

Thx another country after India and Philippines with XBB.2.3 on the lead.