Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses

Lab Invest. 2000 Feb;80(2):171-86. doi: 10.1038/labinvest.3780021.


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.

MeSH terms

  • Animals
  • Apoptosis*
  • Ebolavirus / pathogenicity*
  • Ebolavirus / ultrastructure
  • Endothelium, Vascular / ultrastructure
  • Endothelium, Vascular / virology
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Lymph Nodes / ultrastructure
  • Lymph Nodes / virology
  • Marburgvirus / pathogenicity*
  • Marburgvirus / ultrastructure
  • Microscopy, Electron
  • Monocytes / ultrastructure
  • Monocytes / virology
  • Primates