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

• Published in: iScience Vol. 26; no. 8; p. 107323
• Main Authors: Perez-Valencia, Luis J., Vannella, Kevin M., Ramos-Benitez, Marcos J., Sun, Junfeng, Abu-Asab, Mones, Dorward, David W., Awad, Keytam S., Platt, Andrew, Jacobson, Eliana, Kindrachuk, Jason, Chertow, Daniel S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.08.2023; Elsevier
• Subjects: Cell biology; Immunology; Molecular biology; Virology; Cell biology; Immunology; Molecular biology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107323

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. [Display omitted] •EBOV-shed GP consistently decreased viability of human B, NK, and T cells•B and NK cells exhibited higher susceptibility to shed GP than T cells•Continuous kinetics of shed GP-induced cell death differs by cell type•Shed GP-induced cell death is both caspase dependent and caspase independent Molecular biology; Immunology; Virology; Cell biology.