HV.1 sublineage with ORF1a:T4083M first detected in California, USA (1216 GISAID seqs as of 2023-10-10; All Inhabited Continents)

[alurqu]

There may be a HV.1 sublineage with ORF1a:T4083M (C12513T; NSP8:T141M) first detected in California, USA.

As of 2023-08-30, Cov-Spectrum reports 29 good-quality (34 total) HV.1+ORF1a:4083M sequences. Source: https://cov-spectrum.org/explore/World/AllSamples/AllTimes/variants?variantQuery=nextcladePangoLineage%3AHV.1+%26+ORF1a%3AT4083M&nextcladeQcOverallScoreTo=29&

There are not yet enough sequences in any one country to reliably estimate a growth advantage, but this lineage is a sublineage of a fast parent lineage, has been detected in 4 countries on 3 continents including 3 Canadian provinces and 19 American states, and it has an additional mutation ORF1a:T4083M (aka NSP8:T141M) that Bloom and Neher show as providing a growth advantage in all clades.

As of 2023-08-24, 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_HV.1%2BORF1a_4083M.json?c=gt-ORF1ab_4083&label=id%3Anode_6908889

GISAID query: C12513T, C22033A, C5835T (improved query courtesy of @FedeGueli)

First GISAID sequence: California, USA 2023-07-24

Most Recent GISAID sequence: Ontario, Canada and Quebec, Canada 2023-08-21

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-HV.1+ORF1a_4083M.zip

A CoV-Spectrum list of GISAID EPI ISLs for good-quality sequences is available at gisaid-epi-isl-HV.1+ORF1a_4083M.txt

This proposal has been promoted from pre-proposal https://github.com/sars-cov-2-variants/lineage-proposals/issues/683

Potential effects of the non-synonymous mutation 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 ORF1a:T4083M,

clade,gene,aa_mutation,delta_fitness 20A,ORF1ab,T4083M,1.3672 20B,ORF1ab,T4083M,1.2216 20C,ORF1ab,T4083M,1.308 20E,ORF1ab,T4083M,1.2706 20G,ORF1ab,T4083M,1.5972 20I,ORF1ab,T4083M,0.97347 21C,ORF1ab,T4083M,1.6464 21I,ORF1ab,T4083M,1.2674 21J,ORF1ab,T4083M,1.3126 21K,ORF1ab,T4083M,1.1227 21L,ORF1ab,T4083M,0.62093 22A,ORF1ab,T4083M,0.57972 22B,ORF1ab,T4083M,0.98779 22C,ORF1ab,T4083M,0.64668 22D,ORF1ab,T4083M,0.27632 22E,ORF1ab,T4083M,0.82636 22F,ORF1ab,T4083M,1.0486 23A,ORF1ab,T4083M,0.63056

[FedeGueli]

Just to add i think @corneliusroemer maybe could remember the same mutation was highly homoplasic on AY.4 background back in 2021: https://github.com/cov-lineages/pango-designation/issues/332#issuecomment-999478578

[alurqu]

Now detected on a 4th continent.

[alurqu]

This lineage has really jumped in counts in the last 8 days and has now been reported on all continents with significant human populations.

This lineage also appears to be a major sublineage of but not a majority of HV.1:

[FedeGueli]

Yes it is the one driving HV.,1 very high in growth advantages

[FedeGueli]

368 now . it is the only non flip lineage (ba.2.86 excluded) to be faster than HK.3

[alurqu]

This grown by a factor of 4 to 580 sequences in the last 16 days.

An alternate search (lineage HV.1, AA substitution NSP8_T141M) instead of the nucleotide search also turns up 580 sequences but a slightly different result set that includes a sequence from Austria.

[alurqu]

This lineage continues to grow robustly, but in the USA where it is most common it shows little growth advantage over its parent HV.1. I'm ambivalent over whether to close this issue due to lack of growth advantage or leave it open due to the robust growth and likelihood that this is developing into a large branch of its own.

[FedeGueli]

661 as today with the new update by CovSpectrum its advantage over the parental HV.1 is clear with all the 3 CIs pointing to at least a 5% of advantage. It is also not far from HK.3

[FedeGueli]

793 as today this is how it is doing vs its parent lineage HV.1

[alurqu]

A separately-proposed sublineage of this has been designated HV.1.1 leaving no room for this to be designated.

I am closing this proposal as unplanned.