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。2021 Aug；6（8）：1094-1101。
doi:10.1038/s41564-021-00933-9。 Epub2021Jun23。

Emergence and spread of a SARS-CoV-2 lineage A variant（A.23.1）with altered spike protein in in Uganda

Daniel Lule Bugembe # 1个单击功能区上y V T Phan # 1个单击功能区上Isaac Ssewanyana 2单击功能区上Patrick Semanda 2单击功能区上Hellen Nansumba 2单击功能区上Beatric Dhaala 1个单击功能区上Susan Nabadda 2单击功能区上区域导航工具 3单击功能区上Andrew Rambaut 3单击功能区上Pontiano Kaleebu 1个 4个单击功能区上Matthew Cotten 5 6个
疲劳，疲劳

Emergence and spread of a SARS-CoV-2 lineage A variant（A.23.1）with altered spike protein in in Uganda

Daniel Lule Bugembeet al。 Nat Microbiol。 2021 Aug。

Abstract

Here，we report SARS-Cov-2genomic surveillance from March2020until January2021in Uganda，andlocked East African country with a population of approximately40million people.We report322full SARS-Cov-2genomes from39424reported SARS-Cov-2infections， thus representing0.8%of the reported cases.Phylogenetic analyses of these sequences revealed the emergence of lineage A.23.1 from lineage A.23.Lineage A.23.1represented 88%of the genomes observed in December2020，then100%of the genomes observed in January2021.The A.23.1 lineage was also reported in 26other countries.Although the precise changes in A.23.1differ from those reported in the first three SARS-Cov-2variants of concern（VOCs），the A.23.1 spike-protein-coding region has changes similar to VOCs including a change at position 613，a change in the furin cleavage site that extends the basic amino acid motif and multiple changes in the immunogenic N-terminal domain.Inaddition，the A.23.1 lineage has changes in non-spike protes including，6， ORF8and ORF9that are also altered in other VOCs.The clinical impact of the A.23.1 variant is not yet clear and it has not been designated as a VOC.However，our findings of emergence and spread of this variant indicate that careful monitoring of this variant， together with assessment of the consequences of the spike protein changes for COVID-19vaccine performance，are advisable。

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The authors declare no competing interests。

Figures

Fig.1
Fig.1.SARS-COV-2lineage diversity in Uganda。
从所有高成本sequences到Uganda（n = 322）were lineage-typed using the pangolin resource（https://github.com/cov-lineages/pangolin）。Lineage counts were stratified into four periods:March–May2020（a）；June–August2020（b）；September–November2020（c）；and December2020to January2021（d）。已安装的道路施工规范https://github.com/laserson/squarify）with the size of each sector proportional to the number of genomes；genome numbers are listed with‘n = 。源数据
Fig.2
Fig.2.Maximum-likelihood phylogenetic tree comparing all available complete and high-coverage Uganda sequences（n = 322）。
Strain names are coloured according to the case profile:cases from the community，dark red；prison，orange；truck driver，light brown；return traveller，light blue.The case clusters from prison in Kitgum and Amuru are high lighted in colour boxes in light yellow and light green， respectively.Lineages A.23and A.23.1are indicated.The tree was rooted where lineages A and B were split.Branch length is drawn to the scale of the number of nucleotide substitutions per site，indicated in the lower left；only bootstrap values of major nodes are shown.Source data
Fig.3
Fig.3.Spike protein changes in lineage A.23and A.23.1 relative to the SARS-CoV-2reference strain（NC_045512）encoded protein。
a单击功能区上，The locations of important spike protein features are indicated。b，Each line represents the encoded spike protein sequence from a single genome，ordered by date of sample collection（bottom earliest，top most recent）.Sequences from Amuru in August2020，Kitgum in September2020and Uganda in October，November and December2020/January2021are indicated。列车列车列车停靠站，列车停靠站，列车停靠站，列车停靠站，列车停靠站，列车停靠站，列车停靠站，列车停靠站，列车停靠站，new amino acid）and the labels were placed as close as possible to the substitution。c单击功能区上，Current global temporal distribution of A.23and A.23.1.All available SARS-CoV-2genomes annotated as complete and lineage A from GISAID were retrieveed on4 February 2021and lineage-typed using pangolin and confirmed as A.23and A.23.1by extracting and examining the encoded spiprotein.All new Unda and A.werty在…之前re also included.Genomes were plotted by country and sample collection date.Source data
Fig.4
Fig.4.Protein changes across lineage variants。
All forward open reading frames from the 35early lineage B SARS-CoV-2genomes were translated and processed into44amino acid peptides（with22amino acid overlap），clustered at0.65identity using uclust，aligned with MAAFT and converted into pHMMs using HMMER-3（ref。The presence of each domain and its bit-score（a measure of the similarity between the query sequence and the sequences used for the pHMM）was sought in each set of SARS-COV-2VOC genomes and the 1-mean of the normalized domain bit-scores was plotted across the genome（for example，1-the similarity of the identified query domain to the reference lineage B SARS-COV-2domain）。Domains are coloured by the proteins from which they were derived with the colour code is indicated below the figure.The genome positions of the indicated open reading frames are the following:nsp1:250805；nsp2:8062719；nsp3:272085554；nsp4:855510054；nsp53Cpro:1005510972：1184312091；nsp8Rep:12092，12685；nsp9RNAbp:1268613024；nsp10CysHis:1302513441；RDRP:1344216236；nsp13hel:1623718039；nsp14ExoN:1804019620；nsp15endo:1962120658；nsp16OMT:2065921552；spike:215632584；ORF3a:2539326220；ORF4E:2647252；：2720227387；ORF7a:2739427759；ORF7b:2775627887；ORF8:2789428259；ORF9N:28274，29533；ORF10:2955829712.Note that ORF7b and ORF10are too small to be detected by this analysis method。a单击功能区上，The query set are49mostly Uganda lineage A.23.1genomes。b单击功能区上，All B.1.1.7 full genomes lacking ambiguous nucleotides deposited in GISAID on26 January2021are shown。c单击功能区上，All B.1.351 full genomes lacking ambiguous nucleotides present in GISAID on26 January 2021 are shown。d单击功能区上，All P.1full genomes lacking ambiguous nucleotides present in GISAID on26 January 2021are shown.Source data
扩展数据Fig.1
Extended Data Fig.1.Maximum-likelihood phylogenetic tree comparing Uganda lineage A.23and A.23.1strains to global lineage A.23and A.23.1genomes。
A maximum-likelihood（ML）phylogenetic tree comparing Ugandan A.23and A.23.1（n = 191）with the global A.23and A.23.1（N = 336）。The tree was rooted by the A.23lineage and strains were coloured according to the countries where they were identified.Branch length was drawn to the scale of number of nucleotide substitutions per site and only bootstrap values at the major nodes were shown.The tree was visualised in Figtree.Source data
扩展数据Fig.2
Extended Data Fig.2.Changes in A.23/A.23.1nsp6protein。
The encoded nsp6protein from all Ugandan A.23and A.23.1 genomes gather，aligned and compared to the nsp6protein from GenBankNC_045512.2.Panel a:The locations of important nsp6protein features are indicated based on the analysis of nsp6from Benvenuto et al.Intra_N:intravesicular amino-terminal region，Extra_loop_1:extravesicular loop1，Intra_loop_1:intravesicular loop1，B_del106-108:the region of nsp6deleted in the lineage B VOC genomes，Extra_loop_Big:large extravesicular loop，Intra_loop_2:intravesicularloop2，Extra_loop_2:extravesicularloop_2:extravesicular loop3，Extra_C:carboxy-terminal extra-vesicular portion.All features with‘membrane’indicate membrane-spanning regions of nsp6.Panel b:Each line represents the encoded nsp6protein sequence from a single genome，ordered by date of samples collection（bottom earliest，top most recent）.Coloured markers indicate the positions of amino acid（aa）substitutions from the reference strain sequence，only substitutions observed in multiple genomes are annotated with the annotation（original aa position new aa）and the labels were placed as close as possible to the substitution。源数据
扩展数据Fig.3
Extended Data Fig.3.Changes in A.23/A.23.1 ORF8 protein。
The encoded ORF8 protein from all Ugandan A.23and A.23.1 genomes gather，aligned and compared to the ORF8 protein from GenBankNC_045512.2.Panel a:The locations of important ORF8protein features are indicated based on the analysis of ORF8from Flower et al.Features with‘Beta’indicate beta-sheets，ORF8_specific is a region unique to SARS-COV-2ORF8，CLP_turn:indicatees a cysteine，Leucine，Proline motif essential for a fold in the mature protein，Dimer interface2 indicates the region of the forms the interface between two monomers.Panel b:Each line repreprents the form genome，ordered by date of samples collection（bottom earliest，top most recent）.Coloured markers indicate the positions of amino acid（aa）substitutions from the reference strain sequence，only substitutions observed in multiple genomes are annotated with the annotation（original aa position new aa）and the labels were placed as close as possible to the substitution。源数据
扩展数据Fig.4
Extended Data Fig.4.Changes in A.23/A.23.1 ORF9 protein。
The encoded ORF9 protein from all Ugandan A.23and A.23.1 genomes gather，aligned and compared to the ORF9 protein from GenBankNC_045512.2.Panel a:The locations of important ORF9 protein features are indicated based on the analysis of ORF9 from Chang et al.N-term:amino-terminal extension，NTD:amino-terminal domain，linker:linker region between the NTD and CTD，CTD:carboxy-terminal domain，C-tail:carboxy-terminal extension，Regions with‘Basic’indicate the 4regions enriched in positively charged amino acids.Panel b:Each line represents the encoded ors frome，ordered by date of samples collection（bottom earliest，top most recent）.Coloured markers indicate the positions of amino acid（aa）substitutions from the reference strain sequence，only substitutions observed in multiple genomes are annotated with the annotation（original aa position new aa）and the labels were placed as close as possible to the substitution。源数据
扩展数据Fig.5
扩展数据Fig.5
a，Percentage of total cases reported at the end of January2021were plotted by district（Perc_cases，dark blue bars）.Only districts reporting10 or more cases in the period were included.For the same districts，the percentage of total genomes obtained were plotted（Perc_genomes，light blue bars.The source data for Extended Data Fig.5a can be found in Supplementary Table2。b单击功能区上，District location of cases yielding full genome sequences.The district location in Uganda of cases from which full genome sequences are plotted on a map of Uganda.Districts with>10genomes were marked in red，2-10genomes marked in blue and 1genome marked in grey.Land masses are indiged，in， and lakes are indicate in pale blue.Source data
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