Upregulation of the NKG2D ligand ULBP2 by JC polyomavirus infection promotes immune recognition by natural killer cells

Stephanie Jost; Jenny Ahn; Sarah Chen; Taylor Yoder; Kayitare Eunice Gikundiro; Esther Lee; Simon B Gressens; Kyle Kroll; Melissa Craemer; G Campbell Kaynor; Michelle Lifton; C Sabrina Tan

doi:10.1093/infdis/jiad424

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Upregulation of the NKG2D ligand ULBP2 by JC polyomavirus infection promotes immune recognition by natural killer cells

Journal article

Peer reviewed

Upregulation of the NKG2D ligand ULBP2 by JC polyomavirus infection promotes immune recognition by natural killer cells

Stephanie Jost, Jenny Ahn, Sarah Chen, Taylor Yoder, Kayitare Eunice Gikundiro, Esther Lee, Simon B Gressens, Kyle Kroll, Melissa Craemer, G Campbell Kaynor, …

The Journal of infectious diseases, Vol.229(6), pp.1836-1844

06/15/2024

DOI: 10.1093/infdis/jiad424

PMCID: PMC11175686

PMID: 37774496

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Abstract

BACKGROUND JC polyomavirus(JCPyV) causes progressive multifocal leukoencephalopathy(PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral infections, yet NK cell response to JCPyV infection remains unexplored. METHODS NK and T cell responses against the JCPyV VP1 were compared using intracellular cytokine staining (ICS) upon stimulation with peptide pools. A novel flow cytometry-based assay was developed to determine NK cell killing efficiency of JCPyV-infected astrocyte-derived SVG-A cells. Blocking antibodies were used to identify the specific NK cell receptors in immune recognition of JCPyV-infected cells. RESULTS In about 40% of healthy donors, we detected robust CD107a upregulation and IFN-γ production by NK cells, extending beyond T cell responses. Next, using the NK cell-mediated killing assay, we showed that co-culture of NK cells and JCPyV-infected SVG-A cells leads to a 60% reduction in infection, on average. JCPyV-infected cells had enhanced expression of ULBP2 - a ligand for the activating NK cell receptor NKG2D and addition of NKG2D blocking antibodies decreased NK cell degranulation. CONCLUSION NKG2D-mediated activation of NK cells plays a key role in controlling JCPyV replication and may be a promising immunotherapeutic target to boost NK cell anti-JCPyV activity.

JC polyomavirus

NK cell antiviral immunity

NKG2D

ULBP

Details

Title: Subtitle: Upregulation of the NKG2D ligand ULBP2 by JC polyomavirus infection promotes immune recognition by natural killer cells
Creators: Stephanie Jost - Duke University
Jenny Ahn
Sarah Chen
Taylor Yoder
Kayitare Eunice Gikundiro
Esther Lee
Simon B Gressens
Kyle Kroll - Duke University
Melissa Craemer
G Campbell Kaynor - Biogen (United States)
Michelle Lifton
C Sabrina Tan - University of Iowa, Infectious Diseases
Resource Type: Journal article
Publication Details: The Journal of infectious diseases, Vol.229(6), pp.1836-1844
DOI: 10.1093/infdis/jiad424
PMID: 37774496
PMCID: PMC11175686
NLM abbreviation: J Infect Dis
ISSN: 0022-1899
eISSN: 1537-6613
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 NS116278
Language: English
Electronic publication date: 09/29/2023
Date published: 06/15/2024
Academic Unit: Microbiology and Immunology; Infectious Diseases; Iowa Neuroscience Institute; Internal Medicine
Record Identifier: 9984473208202771

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