Request for B.1.1.482 Sub-lineage

[mattdmem]

Description

Sub-lineage of: B.1.1.482
Earliest sequence: March/April 2021
Most recent sequence: May 2021
Countries circulating: France, UK

Around 11 cases of B.1.1.482 have been discovered in the UK in the last few weeks with a significant amount of new mutations when compared with B.1.1.482 from earlier in the pandemic. These include mutations in Spike and Nsp6 which are also found in many VOCs/VUIs (Table 1).

Genomic Region	Protein	Amino Acid
ORF1a	NSP1	D75G
ORF1a	NSP2	G339S, A411V
ORF1a	NSP3	H342Y, P822L, K927I, N1587S
ORF1a	NSP4	A446V
ORF1a	NSP6	△106-108
ORF1b	NSP12	P323L, S434A
ORF1b	NSP13	T481M
ORF1b	NSP14	A119V
S	Spike	D80G, T95I, G142D, △144, N439K, E484K, D614G, P681H, I1130V, D1139H
M	Membrane	A63T, H125Y
N	Nucleocapsid	I157V, R203K,G204R,

Table 1. Mutations common (n=28) to B.1.1.482 samples from the South Yorkshire Region.
Mutations overlapping B.1.1.482 from North America and Asia highlighted in bold.

Evidence

It's clear from the phylogenetic tree (Figure 1) that these samples have diverged significantly from samples of this lineage earlier in the pandemic. The new UK sequences are clustered in South Yorkshire, UK, and seem to be closely related to a sample sequenced in France of the same lineage (EPI_ISL_1582709) in late march, sharing many of the new mutations.

Figure 1. Maximum likelihood Phylogenetic Tree of 48 B.1.1.482 Samples
A multiple sequence alignment was performed on B.1.1.482 samples using MAFFT v.7.477. The maximum likelihood phylogenetic tree was produced using IQ-TREE v.2.1.2 with GTR + G model and 1,000 ultrafast bootstrap replicates. Red tips denote B.1.1.482 from England.

Genomes

GISAID/Alternative ID	Region	Date of Collection
EPI_ISL_1582709	France	2021-03-28
EPI_ISL_1698537	UK	2021-04-14
EPI_ISL_1857609	UK	2021-04-27
EPI_ISL_1857666	UK	2021-04-27
EPI_ISL_1857753	UK	2021-04-27
EPI_ISL_1857951	UK	2021-04-27
EPI_ISL_1912100	UK	2021-04-26
SHEF-10DA497	UK	2021-04-28
SHEF-10E58AC	UK	2021-04-30
SHEF-10DC3F2	UK	2021-04-30
PHEC-30B21B	UK	Unknown

Authors

Sharon Hsu and Matthew D Parker, Benjamin B Lindsey, Amy State, Peijun Zhang, Benjamin H Foulkes, Stavroula F Louka, Paige Wolverson, Marta Gallis, Hailey R Hornsby, Max Whiteley, Samantha E Hansford1, Nasar Ali, Oscar Shepherdson, Salma Afsar, Katie Johnson, Alexander J Keeley, Joe Heffer, Nikki Smith, David G Partridge, Alison Cope, Michael Ankcorn, Mohammad Raza, Cariad Evans, The COVID-19 UK Genomics Consortium, Thushan I de Silva

It would be great if this child of B.1.1.482 is assigned a lineage definition for easier identification.

Thanks

[grovesn]

also QEUH-148F257, QEUH-14C1E55, QEUH-144D7A1. These are a separate cluster but the same spike profile.

[mattdmem]

@grovesn Thanks! These look more similar to the French one

[grovesn]

[chrisruis]

Hi @mattdmem thanks for submitting this. We've added this as lineage AV.1 (an alias of B.1.1.482.1 as the parental B.1.1.482 lineage already has the maximum of 3 sublevels in it's lineage name) in 1.2.1

I've included samples England/QEUH-148F257/2021 and England/QEUH-14C1E55/2021 that @grovesn added above. We've introduced a requirement for designated sequences to have <5% ambiguities in the coding regions - England/QEUH-144D7A1/2021 is a little above this so wasn't included in the designations. I haven't yet added SHEF-10E58AC and SHEF-10DC3F2 to the designations as I can't find them in the current alignments to check their ambiguities - I'll have another look in a couple of days and hopefully add them in then

[mattdmem]

@chrisruis

Updated list of samples that fall in this sub-lineage:

ALDP-1543D8A
ALDP-154D5B5
ALDP-1555F07
ALDP-1557F6F
ALDP-1558E25
ALDP-155C6DE
ALDP-155C86F
CAMC-1507EE9
MILK-1541FD1
MILK-154CAC6
MILK-155DA68
NORT-1BA57A0
PHEC-30B21B
QEUH-153D6F1
QEUH-1540F5A
QEUH-1541092
QEUH-154128D
QEUH-1543115
SHEF-10DA497
SHEF-10DC3F2
SHEF-10E58AC

[MattBashton]

Just to add these two sequences also look to be part of this sub-lineage, but have in addition an ORF3a deletion via frameshift deletion: c.766_769del:p.V256Ifs*3 (26158 26161 GTTA -) :

NORT-1BB90F9
NORT-1BB9132