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HGNC Genes

SARS-CoV-2 proteins

ORF3a (1)


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    ADNKA overcomes SARS-CoV2-mediated NK cell inhibition through non-spike antibodies

    Authors: Ceri A Fielding; Pragati Sabberwal; James C Williamson; Edward JD Greenwood; Edward Crozier; Wioleta Zelek; Jeffrey Seow; Carl Graham; Isabella Huettner; Jonathan Edgeworth; Brian Paul Morgan; Kristin Ladell; Matthias Eberl; Ian R Humphreys; Blair Merrick; Sam J Wilson; Paul J Lehner; Edward Wang; Richard J Stanton

    doi:10.1101/2021.04.06.438630 Date: 2021-04-06 Source: bioRxiv

    SARS-CoV-2 antagonises the cellular interferon response, but whether the virus manipulates cellular immunity is unclear. An unbiased proteomic approach to determine how cell surface protein expression is altered on SARS-CoV-2-infected MESHD lung epithelial cells showed downregulation of activating NK cell ligands: B7-H6 HGNC, MICA HGNC, ULBP2 HGNC, and Nectin1 HGNC, but no effect on surface MHC-I expression. NK ligand downregulation correlated with a reduction in NK cell activation by infected cells, and was overcome by antibody-dependent NK cell activation (ADNKA). Depletion of spike-specific antibodies confirmed their dominant role in virus neutralisation, but these antibodies played only a minor role in ADNKA compared to antibodies to other viral proteins, including ORF3a PROTEIN, Membrane, and Nucleocapsid. In contrast, ADNKA induced following vaccination was focussed solely on spike, was weaker than ADNKA following natural infection, and was not boosted by the second dose. These insights have important implications for understanding disease progression, vaccine efficacy, and vaccine design.

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MeSH Disease
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SARS-CoV-2 Proteins


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