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

Abstract

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.

• Authors: T W Geisbert, L E Hensley, T R Gibb, K E Steele, N K Jaax, P B Jahrling
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 80 Issue 2 Pg. 171-86 (Feb 2000) ISSN: 0023-6837 [Print] United States
• PMID: 10701687 (Publication Type: Journal Article)

Topics

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