Evidence map›Paper›PMID 36350154›Full record

ArticleJournal of virology2022

The P681H Mutation in the Spike Glycoprotein of the Alpha Variant of SARS-CoV-2 Escapes IFITM Restriction and Is Necessary for Type I Interferon Resistance.

Maria Jose Lista, Helena Winstone, Harry D Wilson, Adam Dyer, Suzanne Pickering, Rui Pedro Galao, Giuditta De Lorenzo, Vanessa M Cowton, Wilhelm Furnon, Nicolas Suarez and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
8.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 67 citations in OpenAlex.

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  5. Clade C MERS-CoV camel strains vary in protease utilization during viral entry.Proceedings of the National Academy of Sciences of the United States of America · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Maria Jose Lista *Department of Infectious Diseases, King's College London, London, United Kingdom.
Helena Winstone *Department of Infectious Diseases, King's College London, London, United Kingdom.
Harry D WilsonDepartment of Infectious Diseases, King's College London, London, United Kingdom.ORCID 0000-0002-3185-1073
Adam DyerDepartment of Infectious Diseases, King's College London, London, United Kingdom.
Suzanne PickeringDepartment of Infectious Diseases, King's College London, London, United Kingdom.
Rui Pedro GalaoDepartment of Infectious Diseases, King's College London, London, United Kingdom.
Giuditta De LorenzoMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.ORCID 0000-0002-2736-8740
Vanessa M CowtonMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Wilhelm FurnonMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Nicolas SuarezMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Richard OrtonMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Massimo PalmariniMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Arvind H PatelMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.ORCID 0000-0003-4600-2047
Luke SnellCentre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.ORCID 0000-0002-6263-9497
Gaia NebbiaCentre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Chad SwansonDepartment of Infectious Diseases, King's College London, London, United Kingdom.ORCID 0000-0002-6650-3634
Stuart J D NeilDepartment of Infectious Diseases, King's College London, London, United Kingdom.ORCID 0000-0003-3306-5831
King's College London · GBMRC University of Glasgow Centre for Virus Research · GBGuy's and St Thomas' NHS Foundation Trust · GB

Funding

Medical Research Council MC_UU_12014/2Medical Research Council MC_UU12014/2Medical Research Council MR/N013700/1Medical Research Council MR/S000844/1Medical Research Council MR/W005611/1Medical Research Council MR/W025140/1Wellcome Trust 206369/Z/17/ZWellcome Trust 207442/Z/17/ZWellcome Trust WT098049AIA
6 · The paper itself

Abstract

The appearance of new dominant variants of concern (VOC) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) threatens the global response to the coronavirus disease 2019 (COVID-19) pandemic. Of these, the alpha variant (also known as B.1.1.7), which appeared initially in the United Kingdom, became the dominant variant in much of Europe and North America in the first half of 2021. The spike (S) glycoprotein of alpha acquired seven mutations and two deletions compared to the ancestral virus, including the P681H mutation adjacent to the polybasic cleavage site, which has been suggested to enhance S cleavage. Here, we show that the alpha spike protein confers a level of resistance to beta interferon (IFN-β) in human lung epithelial cells. This correlates with resistance to an entry restriction mediated by interferon-induced transmembrane protein 2 (IFITM2) and a pronounced infection enhancement by IFITM3. Furthermore, the P681H mutation is essential for resistance to IFN-β and context-dependent resistance to IFITMs in the alpha S. P681H reduces dependence on endosomal cathepsins, consistent with enhanced cell surface entry. However, reversion of H681 does not reduce cleaved spike incorporation into particles, indicating that it exerts its effect on entry and IFN-β downstream of furin cleavage. Overall, we suggest that, in addition to adaptive immune escape, mutations associated with VOC may well also confer a replication and/or transmission advantage through adaptation to resist innate immune mechanisms.

Indexed as

COVID-19Interferon Type ICell LineFurinHumansMembrane ProteinsMutationRNA-Binding ProteinsSARS-CoV-2Spike Glycoprotein, CoronavirusFurinIFITM2 protein, humanIFITM3 protein, humanInterferon Type IMembrane ProteinsRNA-Binding ProteinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2furin cleavage siteIFITMSARS-CoV-2type 1 interferonVOC

Identifiers

PMID36350154
PMCPMC9749455
OpenAlexW4308634906

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.