Comprehensive Genome Analysis of 6,000 USA SARS-CoV-2 Isolates Reveals Haplotype Signatures and Localized Transmission Patterns by State and by Country

Shen, Lishuang; Bard, Jennifer Dien; Biegel, Jaclyn A.; Judkins, Alexander R.; Gai, Xiaowu

doi:10.3389/fmicb.2020.573430

Cited by 17 publications

(13 citation statements)

References 9 publications

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“…Sequence analysis of Russian SARS-CoV-2 isolates, including those from other countries, has revealed a set of seven common mutations in S and N proteins, suggesting their multiple import to Russia, local circulation and varying patterns of spread [ 36 ]. Meta-analysis of SARS-CoV-2 isolates within the USA has also identified over 900 unique variants in at least three samples [ 55 ]. These included 487 missense and 348 synonymous mutations, four in-frame deletions, five stop codon insertions/deletions and 66 intergenic recombinations.…”

Section: Discussionmentioning

confidence: 99%

Comparative Sequence Analysis of SARS-CoV-2 Suggests Its High Transmissibility and Pathogenicity

2021

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Aim: Because the highly pathogenic SARS-CoV-2 is newly introduced to humans, we aimed to understand the unique features of its genome and proteins, crucial for high transmissibility and disease severity. Materials & methods: The available genome and protein sequences of SARS-CoV-2 with known human and nonhuman CoV were analyzed using multiple sequence alignment programs. Results: Our analysis revealed some unique mutations in SARS-CoV-2 spike, ORF1a/b, ORF3a/3b and ORF8. The most interesting ones were in the spike angiotensin-converting enzyme 2 receptor binding-motif and generation of a furin-like cleavage site as well as deletions of ORF3a ‘diacidic motif’ and the entire ORF3b. Conclusion: Our data suggest that SARS-CoV-2 has diverged from SARS-CoV-1 but is most close to bat-SL-CoV. Unique mutations in spike and ORF3a/b proteins strongly endorse its adaptive evolution, enhanced infectivity and severe pathogenesis in humans.

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Section: Discussionmentioning

confidence: 99%

Comparative Sequence Analysis of SARS-CoV-2 Suggests Its High Transmissibility and Pathogenicity

2021

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“…Full-length SARS-CoV-2 sequences have been periodically downloaded from GISAID and NCBI GenBank. They are combined with sequences from CHLA patients, annotated, and curated using bioinformatics tools previously described [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications

Shen

Bard

Triche

et al. 2021

Emerging Microbes & Infections

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Mutations in the SARS-CoV-2 Membrane (M) gene are relatively uncommon. The M gene encodes the most abundant viral structural protein, and is implicated in multiple viral functions, including initial attachment to the host cell via heparin sulphate proteoglycan, viral protein assembly in conjunction with the N and E genes, and enhanced glucose transport. We have identified a recent spike in the frequency of reported SARS-CoV-2 genomes carrying M gene mutations. This is associated with emergence of a new sub-B.1 clade, B.1.I82T, defined by the previously unreported M:I82T mutation within TM3, the third of three membrane spanning helices implicated in glucose transport. The frequency of this mutation increased in the USA from 0.014% in October 2020 to 1.62% in February 2021, a 116-fold change. While constituting 0.7% of the isolates overall, M:I82T sub-B.1 lineage accounted for 14.4% of B.1 lineage isolates in February 2021, similar to the rapid initial increase previously seen with the B.1.1.7 and B.1.429 lineages, which quickly became the dominant lineages in Europe and California over a period of several months. A similar increase in incidence was also noted in another related mutation, V70L, also within the TM2 transmembrane helix. These M mutations are associated with younger patient age (4.6 to 6.3 years). The rapid emergence of this B.1.I82T clade, recently named Pangolin B.1.575 lineage, suggests that this M gene mutation is more biologically fit, perhaps related to glucose uptake during viral replication, and should be included in ongoing genomic surveillance efforts and warrants further evaluation for potentially increased pathogenic and therapeutic implications.

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mentioning

confidence: 99%

Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications

Shen

Bard

Triche

et al. 2021

Preprint

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Mutations in the SARS-CoV-2 Membrane (M) gene are relatively uncommon. The M gene encodes the most abundant viral structural protein, and is implicated in multiple viral functions, including initial attachment to the host cell via heparin sulfate proteoglycan, viral protein assembly in conjunction with the N and E genes, and enhanced glucose transport. We have identified a recent spike in the frequency of reported SARS-CoV-2 genomes carrying M gene mutations. This is associated with emergence of a new sub-B.1 clade defined by the previously unreported M:I82T mutation within TM3, the third of three membrane spanning helices implicated in glucose transport. The frequency of this mutation increased in the USA from 0.014% in October 2020 to 1.62% in February 2021, a 116-fold change. While constituting 0.7% of the isolates overall, M:I82T sub-B.1 lineage accounted for 14.4% of B.1 lineage isolates in February 2021, similar to the rapid initial increase previously seen with the B.1.1.7 and B.1.429 lineages, which quickly became the dominant lineages in Europe and California over a period of several months. A similar increase in incidence was also noted in another related mutation, V70L, also within the TM2 transmembrane helix. The rapid emergence of this sub-B.1 clade with recurrent I82T mutation suggests that this M gene mutation is more biologically fit, perhaps related to glucose uptake during viral replication, and should be included in ongoing genomic surveillance efforts and warrants further evaluation for potentially increased pathogenic and therapeutic implications.

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Comprehensive Genome Analysis of 6,000 USA SARS-CoV-2 Isolates Reveals Haplotype Signatures and Localized Transmission Patterns by State and by Country

Cited by 17 publications

References 9 publications

Comparative Sequence Analysis of SARS-CoV-2 Suggests Its High Transmissibility and Pathogenicity

Comparative Sequence Analysis of SARS-CoV-2 Suggests Its High Transmissibility and Pathogenicity

Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications

Emerging variants of concern in SARS-CoV-2 membrane protein: a highly conserved target with potential pathological and therapeutic implications

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