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

Thomas Geisbert, Lisa E. Hensley, Tammy R. Gibb, Keith E. Steele, Nancy K. Jaax, Peter B. Jahrling

Research output: Contribution to journalArticle

229 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)171-186
Number of pages16
JournalLaboratory Investigation
Volume80
Issue number2
StatePublished - Feb 2000
Externally publishedYes

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Marburgvirus
Ebolavirus
Apoptosis
Lymphocytes
Infection
Transmission Electron Microscopy
Lymph Nodes
Mononuclear Phagocyte System
Lymphopenia
DNA Nucleotidylexotransferase
Viral Proteins
Plasma Cells
Primates
Population
In Vitro Techniques
Blood Cells
Immunohistochemistry
Macrophages
Viruses
T-Lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Geisbert, T., Hensley, L. E., Gibb, T. R., Steele, K. E., Jaax, N. K., & Jahrling, P. B. (2000). Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. Laboratory Investigation, 80(2), 171-186.

Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. / Geisbert, Thomas; Hensley, Lisa E.; Gibb, Tammy R.; Steele, Keith E.; Jaax, Nancy K.; Jahrling, Peter B.

In: Laboratory Investigation, Vol. 80, No. 2, 02.2000, p. 171-186.

Research output: Contribution to journalArticle

Geisbert, T, Hensley, LE, Gibb, TR, Steele, KE, Jaax, NK & Jahrling, PB 2000, 'Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses', Laboratory Investigation, vol. 80, no. 2, pp. 171-186.
Geisbert T, Hensley LE, Gibb TR, Steele KE, Jaax NK, Jahrling PB. Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. Laboratory Investigation. 2000 Feb;80(2):171-186.
Geisbert, Thomas ; Hensley, Lisa E. ; Gibb, Tammy R. ; Steele, Keith E. ; Jaax, Nancy K. ; Jahrling, Peter B. / Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. In: Laboratory Investigation. 2000 ; Vol. 80, No. 2. pp. 171-186.
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