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Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2.

ABSTRACT: As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid deletion encompassing a furin recognition motif and S1/S2 cleavage site. We elucidate the structure, function and molecular dynamics of this spike providing mechanistic insight into how the deletion correlates to viral cell tropism, ACE2 receptor binding and infectivity of this SARS-CoV-2 variant. Our results reveal long-range allosteric communication between functional domains that differ in the wild-type and the deletion variant and support a view of SARS-CoV-2 probing multiple evolutionary trajectories in distinct cell types within the same infected host.

SUBMITTER: Gupta K

PROVIDER: S-EPMC8752678 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2.

Gupta Kapil K Toelzer Christine C Williamson Maia Kavanagh MK Shoemark Deborah K DK Oliveira A Sofia F ASF Oliveira A Sofia F ASF Matthews David A DA Almuqrin Abdulaziz A Staufer Oskar O Yadav Sathish K N SKN Borucu Ufuk U Garzoni Frederic F Fitzgerald Daniel D Spatz Joachim J Mulholland Adrian J AJ Davidson Andrew D AD Schaffitzel Christiane C Berger Imre I

Nature communications 20220111 1

As the global burden of SARS-CoV-2 infections escalates, so does the evolution of viral variants with increased transmissibility and pathology. In addition to this entrenched diversity, RNA viruses can also display genetic diversity within single infected hosts with co-existing viral variants evolving differently in distinct cell types. The BriSΔ variant, originally identified as a viral subpopulation from SARS-CoV-2 isolate hCoV-19/England/02/2020, comprises in the spike an eight amino-acid del ...[more]

PMID: 35017512

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Dataset Information

Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2.

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Structural insights in cell-type specific evolution of intra-host diversity by SARS-CoV-2.

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