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
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.
