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

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: iScience, Vol 26, Iss 8, Pp 107323- (2023)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2023.107323
Popis: 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.
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