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
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.
iScience. 2023 Jul 11;26(8):107323. doi: 10.1016/j.isci.2023.107323. eCollection 2023 Aug 18.
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 . 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.
淋巴细胞耗竭是埃博拉病毒（EBOV）疾病的一个显著特征。EBOV糖蛋白（GP）的胞外域从受感染细胞表面裂解下来，以脱落型GP的形式进入循环。为了验证脱落型GP诱导淋巴细胞死亡这一假说，我们用脱落型GP培养原代人B细胞、自然杀伤（NK）细胞或T细胞。我们发现，脱落型GP可可靠地降低不同供体的B细胞、NK细胞和T细胞活力。B细胞和NK细胞比T细胞表现出更高的敏感性。持续监测显示，脱落型GP在4小时开始杀死B细胞和NK细胞，在5小时开始杀死T细胞。我们还证明，脱落型GP诱导的淋巴细胞死亡既可以是半胱天冬酶依赖性的，也可以是半胱天冬酶非依赖性的。我们的数据证明，脱落型GP对淋巴细胞的细胞毒性作用可能导致EBOV疾病，并突出了进一步研究以阐明脱落型GP诱导死亡机制的必要性。
