PXD025000

PXD025000 is an original dataset announced via ProteomeXchange.

Title	SARS-CoV2 manipulates multiple NK ligands and inhibits NK activation, but this can be overcome by ADNKA, which is strongly activated by non-Spike targeting antibodies
Description	SARS-CoV2 is recognised the antagonise the interferon response, and functioning interferon responses are critical in determining the severity of disease. However, whether the virus antagonises cellular immunity has not been determined. We used quantitative plasma membrane proteomics in lung epithelial cells to investigate viral manipulation of cell surface ligands, revealing that SARS-CoV2 does not affect HLA-I levels, but downregulates B7-H6, MICA, ULBP2, and Nectin1. Downregulation of these activating NK ligands correlated with a reduction in NK activation in response to infected cells. However, this activation could be overcome through antibody dependent NK activation (ADNKA). Surprisingly, monoclonal anti-spike antibodies were relatively poor activators of ADNKA, however expression of additional viral proteins, including ORF3a and Nucleocapsid, also led to NK activation following addition of antibodies. Furthermore, depletion of Spike antibodies revealed that while the neutralising response was dominated by anti-spike antibodies, these played a minor role in ADNKA against infected cells. Finally, we showed that anti-spike antibodies do mediate ADNKA following vaccination, but that by relying solely on spike to prime ADNKA, this response is considerably weaker than the responses seen following natural infection, and are not boosted by a second vaccine dose. Thus, the addition of extra viral proteins such as nucleocapsid to vaccines may recruit additional effector functions more strongly, reducing the impact of spike mutations on vaccine escape.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:03.350.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD025000
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	James Williamson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue; monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-25 03:42:31	ID requested
1	2022-05-26 00:15:35	announced
⏵ 2	2023-11-14 08:52:03	announced	2023-11-14: Updated project metadata.

10.6019/PXD025000;

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: SARS-CoV2, NK Ligands, ADNKA

Paul Lehner
contact affiliation	Cambridge Institute of Therapeutic Immunology and Infectious Disease, Cambridge, UK
contact email	pjl30@cam.ac.uk
lab head
James Williamson
contact affiliation	University of Cambridge
contact email	jcw76@cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025000
     1. Label: PRIDE project
     2. Name: SARS-CoV2 manipulates multiple NK ligands and inhibits NK activation, but this can be overcome by ADNKA, which is strongly activated by non-Spike targeting antibodies