KP.3.1 + S:ins16_MPVF, ORF1a:T1854I (273 seq, Aug 9)

[ryhisner]

Description
Sub-lineage of: KP.3.1
Earliest sequence: 2024-4-28, Spain, Basque Country — EPI_ISL_19095498
Most recent sequence: 2024-6-21, Japan, Saitama —EPI_ISL_19218509
Continents circulating: Europe (97), North America (3), Asia (1)
Countries circulating: Spain (93), USA (3), Portugal (2), Canary Islands (1), France (1—traveler to USA), Japan (1), Scotland (1)
Number of Sequences: 101
GISAID Nucleotide Query: C897A, C5826T, C18570T
CovSpectrum Query: Nextcladepangolineage: KP.3* & [2-of: C5826T, C18570T]
Substitutions on top of KP.3.1:
Spike: ins16MPFV (in place of MPLF)
ORF1a: T1854I (NSP3_T1036I)
Nucleotide: C5826T, C18570T, ins21608_TCATGCCGGTGT (C→G at nuc 9, replacing ins21608_TCATGCCGCTGT)

Phylogenetic Order of Mutations: C18570T → C5826T (ORF1a:T1854I)

USHER Tree
https://nextstrain.org/fetch/raw.githubusercontent.com/ryhisner/jsons2/main/KP.3.1_ins16_MPVF__T1854I_80seq.json?label=id:node_5612770

Evidence
Fortunately, this mutation in the insertion is accompanied by another nucleotide mutation (C5826T) that, as far as I can tell, is exclusive to this lineage, and which every sequence in this lineage possesses. Only 64 of the 79 sequences in this branch register the insertion, but 100% of these have MPVF. I think it's safe to assume that the remaining 15 sequences, which failed to register the insertion, have the same mutation within the insertion.

Notably, there is a 5-sequence branch here that has S:R190S, an old Gamma mutation that adds a glycan at N188. One of these sequences looks like a coinfection with KP.2.2. Since it has the MPVF insertion, S:F59L, S:R190S, R346T, and K1266R and lacks Q493E, the only way it could be a recombinant is if it had three breakpoints, one between S:16 and S:59, another between S:59 and S:R190S, and another between S:R190S and S:R346T. Seems unlikely.

This involves a C->G nucleotide mutation (the rarest of all nuc mutations) in the ninth nucleotide of the S:ins16_MPLF insertion, changing it to MPVF. The insertion's nucleotide sequences changes from TCATGCCGCTGT → TCATGCCGGTGT.

It's mostly in Spain but has been detected in 10 different regions of Spain (Andalusia, Asturias, Basque Country, Catalunya, Extremadura, Galicia, Guadalajara, Madrid, Murcia, and Navarra), and sequences from France, Scotland and the US show it's not just an Iberian phenomenon.

Genomes

Genomes

EPI_ISL_19095498, EPI_ISL_19140785-19140786, EPI_ISL_19140790-19140793, EPI_ISL_19145543, EPI_ISL_19145554, EPI_ISL_19147551, EPI_ISL_19151048, EPI_ISL_19157478, EPI_ISL_19167871, EPI_ISL_19167883, EPI_ISL_19175464, EPI_ISL_19175492, EPI_ISL_19178537, EPI_ISL_19179530-19179531, EPI_ISL_19185407, EPI_ISL_19185409, EPI_ISL_19185422, EPI_ISL_19185514, EPI_ISL_19187594, EPI_ISL_19187889, EPI_ISL_19187957, EPI_ISL_19188434, EPI_ISL_19189122, EPI_ISL_19189978, EPI_ISL_19190778-19190779, EPI_ISL_19193934, EPI_ISL_19193948, EPI_ISL_19194008, EPI_ISL_19194798, EPI_ISL_19194811, EPI_ISL_19194836, EPI_ISL_19194853, EPI_ISL_19194860, EPI_ISL_19194896, EPI_ISL_19194919, EPI_ISL_19194934, EPI_ISL_19194958, EPI_ISL_19194999, EPI_ISL_19195010, EPI_ISL_19195026, EPI_ISL_19195033, EPI_ISL_19195088, EPI_ISL_19195387, EPI_ISL_19195929, EPI_ISL_19195962, EPI_ISL_19196521, EPI_ISL_19196525, EPI_ISL_19196971, EPI_ISL_19196977, EPI_ISL_19196980, EPI_ISL_19197892, EPI_ISL_19197903-19197904, EPI_ISL_19198470, EPI_ISL_19201367-19201368, EPI_ISL_19201405, EPI_ISL_19201409, EPI_ISL_19201414, EPI_ISL_19201417, EPI_ISL_19201420, EPI_ISL_19201425, EPI_ISL_19201429, EPI_ISL_19201439, EPI_ISL_19201533, EPI_ISL_19201538-19201539, EPI_ISL_19201630, EPI_ISL_19202190, EPI_ISL_19203533, EPI_ISL_19204048-19204049, EPI_ISL_19209676, EPI_ISL_19210114

[FedeGueli]

Thanks @ryhisner i have noticed that on covspectrum but assumed it was artifact, thx for looking into it

[FedeGueli]

This can compete with KP.3.1.1

see https://cov-spectrum.org/explore/Spain/AllSamples/Past3M/variants?%2FAllSamples%2FPast3M%2Fvariants%3FnextcladePangoLineage=JN.1*&nucMutations=C897A%2CC5826T%2CC18570T&nucMutations1=C12616T%2CA13121T&analysisMode=CompareToBaseline&

[FedeGueli]

the orf1a mutation should correspond to PLPro_T291I = NSP3_T1036I

[FedeGueli]

82 on gisaid now : C897A, C5826T, C18570T

[FedeGueli]

102 is growing quite fast

[ryhisner]

Yeah, growing fast in Spain. One sequence has now appeared in Japan. The real test will be to see if it grows anywhere outside of Spain. It hasn't done so yet.