The Ebola-Glycoprotein Modulates the Function of Natural Killer Cells

Frontiers in Immunology
Avishay EdriAngel Porgador

Abstract

The Ebola virus (EBOV) uses evasion mechanisms that directly interfere with host T-cell antiviral responses. By steric shielding of human leukocyte antigen class-1, the Ebola glycoprotein (GP) blocks interaction with T-cell receptors (TCRs), thus rendering T cells unable to attack virus-infected cells. It is likely that this mechanism could promote increased natural killer (NK) cell activity against GP-expressing cells by preventing the engagement of NK inhibitory receptors; however, we found that primary human NK cells were less reactive to GP-expressing HEK293T cells. This was manifested as reduced cytokine secretion, a reduction in NK degranulation, and decreased lysis of GP-expressing target cells. We also demonstrated reduced recognition of GP-expressing cells by recombinant NKG2D and NKp30 receptors. In accordance, we showed a reduced monoclonal antibody-based staining of NKG2D and NKp30 ligands on GP-expressing target cells. Trypsin digestion of the membrane-associated GP led to a recovery of the recognition of membrane-associated NKG2D and NKp30 ligands. We further showed that membrane-associated GP did not shield recognition by KIR2DL receptors; in accordance, GP expression by target cells significantly perturbed signa...Continue Reading

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Citations

May 6, 2019·Viruses·Michelle L PleetFatah Kashanchi
Jan 31, 2020·Frontiers in Immunology·Martin VillalbaDelphine Gitenay
Mar 27, 2020·Frontiers in Cellular and Infection Microbiology·Muhammed IraqiAngel Porgador
Nov 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Yelena Kravtsova-IvantsivAaron Ciechanover
Aug 14, 2020·Current Opinion in Virology·Carlos Diaz-Salazar, Joseph C Sun
Jan 31, 2021·Communications Biology·Yariv GreenshpanAngel Porgador
Aug 24, 2021·Current Opinion in Pharmacology·Goutam BanerjeePratik Banerjee

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Methods Mentioned

BETA
transfection
column chromatography
FCS
flow cytometry
ELISA
Assay
immunoprecipitation
electrophoresis

Software Mentioned

ImageStream
Office
Excel
FlowJo

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