Ebola virus shed glycoprotein is toxic to human T, B, and natural killer lymphocytes

Luis J. Perez-Valencia; Kevin M. Vannella; Marcos J. Ramos-Benitez; Junfeng Sun; Mones Abu-Asab; David W. Dorward; Keytam S. Awad; Andrew Platt; Eliana Jacobson; Jason Kindrachuk; Daniel S. Chertow

iScience (Aug 2023)

Ebola virus shed glycoprotein is toxic to human T, B, and natural killer lymphocytes

Luis J. Perez-Valencia,
Kevin M. Vannella,
Marcos J. Ramos-Benitez,
Junfeng Sun,
Mones Abu-Asab,
David W. Dorward,
Keytam S. Awad,
Andrew Platt,
Eliana Jacobson,
Jason Kindrachuk,
Daniel S. Chertow

Affiliations

Luis J. Perez-Valencia: Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kevin M. Vannella: Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Marcos J. Ramos-Benitez: Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Junfeng Sun: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Mones Abu-Asab: Section of Histopathology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
David W. Dorward: Microscopy Unit, Research Technology Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
Keytam S. Awad: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Andrew Platt: Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Eliana Jacobson: Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Jason Kindrachuk: Laboratory of Emerging Viruses, Department of Medical Microbiology, University of Manitoba, Winnipeg MB R3E 0J9, Canada
Daniel S. Chertow: Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 8
p. 107323

Abstract

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Summary: Lymphocyte depletion is a distinctive feature of Ebola virus (EBOV) disease. The ectodomain of EBOV glycoprotein (GP) is cleaved off the surface of infected cells into circulation as shed GP. To test the hypothesis that shed GP induces lymphocyte death, we cultured primary human B, NK, or T cells with shed GP in vitro. We found that shed GP dependably decreased B, NK, and T cell viability across donors. B and NK cells exhibited higher susceptibility than T cells. Continuous monitoring revealed shed GP began to kill B and NK cells by 4 h and T cells by 5 h. We also demonstrated that shed GP-induced lymphocyte death can be both caspase dependent and caspase independent. Our data are evidence that the cytotoxic effect of shed GP on lymphocytes may contribute to EBOV disease and highlight the need for further research to clarify mechanisms of shed GP-induced death.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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