Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses
Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses
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DOI：
10.1038/labinvest.3780021
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发表时间：
2000-02-01
影响因子：
5
通讯作者：
Jahrling, PB
中科院分区：
文献类型：
--
作者：
Geisbert, TW;Hensley, LE;Jahrling, PB
细胞凋亡的诱导已被证明在感染期间与许多不同的病毒。在这项研究中，我们使用透射电子显微镜（TEM）和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记研究埃博拉病毒和马尔堡病毒在体外和体内感染过程中对不同细胞群凋亡的影响。对18只在濒死状态下处死的丝状病毒感染非人灵长类动物的组织进行了评价。在所有检查的组织中均观察到凋亡淋巴细胞。丝状病毒复制发生在单核吞噬细胞系统的细胞和其他有充分记录的细胞目标TEM和免疫组织化学，但没有证据表明在淋巴细胞中复制。除胞浆内病毒包涵体外，丝状病毒感染的细胞在形态上正常或坏死，但未表现出细胞凋亡特征的超微结构变化。在淋巴结中，丝状病毒抗原与凋亡淋巴细胞共定位。对淋巴结中细胞群的检查显示，在丝状病毒感染的动物中，巨噬细胞数量增加，同时CD8（+）T细胞和浆细胞减少。这种消耗在感染埃博拉病毒扎伊尔亚型的动物中特别引人注目。此外，细胞凋亡证明在体外丝状病毒感染的人外周血单核细胞的淋巴细胞通过TEM。这些发现表明，与丝状病毒感染相关的淋巴细胞减少症和淋巴耗竭是由多种因素诱导的淋巴细胞凋亡引起的，这些因素可能包括丝状病毒感染或活化细胞释放各种化学介质、成纤维细胞网状细胞管道系统受损以及可能受到病毒蛋白的刺激。
Induction of apoptosis has been documented during infection with a number of different viruses. In this study, we used transmission electron microscopy (TEM) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling to investigate the effects of Ebola and Marburg viruses on apoptosis of different cell populations during in vitro and in vivo infections. Tissues from 18 filovirus-infected nonhuman primates killed in extremis were evaluated. Apoptotic lymphocytes were seen in all tissues examined. Filoviral replication occurred in cells of the mononuclear phagocyte system and other well-documented cellular targets by TEM and immunohistochemistry, but there was no evidence of replication in lymphocytes. With the exception of intracytoplasmic viral inclusions, filovirus-infected cells were morphologically normal or necrotic, but did not exhibit ultrastructural changes characteristic of apoptosis. In lymph nodes, filoviral antigen was co-localized with apoptotic lymphocytes. Examination of cell populations in lymph nodes showed increased numbers of macrophages and concomitant depletion of CD8(+) T cells and plasma cells in filovirus-infected animals. This depletion was particularly striking in animals infected with the Zaire subtype of Ebola virus. In addition, apoptosis was demonstrated in vitro in lymphocytes of filovirus-infected human peripheral blood mononuclear cells by TEM. These findings suggest that lymphopenia and lymphoid depletion associated with filoviral infections result from lymphocyte apoptosis induced by a number of factors that may include release of various chemical mediators from filovirus-infected or activated cells, damage to the fibroblastic reticular cell conduit system, and possibly stimulation by a viral protein.