Proteomics

Dataset Information

0

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


ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

DISEASE(S): Covid-19

SUBMITTER: James Williamson  

LAB HEAD: Paul Lehner

PROVIDER: PXD025000 | Pride | 2022-05-26

REPOSITORIES: Pride

Dataset's files

Source:

Similar Datasets

2013-11-18 | E-GEOD-50123 | biostudies-arrayexpress
2013-11-18 | GSE50123 | GEO
2013-01-23 | PRD000666 | Pride
2022-02-25 | GSE185989 | GEO
2014-01-22 | E-GEOD-50120 | biostudies-arrayexpress
2013-11-18 | GSE50122 | GEO
2013-11-18 | E-GEOD-50122 | biostudies-arrayexpress
2014-01-22 | GSE50120 | GEO
2021-05-31 | GSE171080 | GEO
2021-09-01 | GSE178566 | GEO