Lymphocyte death in a mouse model of ebola virus infection

Steven B. Bradfute, Denise R. Braun, Joshua D. Shamblin, Joan B. Geisbert, Jason Paragas, Aura Garrison, Lisa E. Hensley, Thomas W. Geisbert

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Background. A striking feature of Zaire Ebola virus (ZEBOV) infection in nonhuman primates is the rapid depletion of T and NK lymphocytes by apoptosis. In a mouse model of ZEBOV infection, lymphocyte death is a prominent finding; however, the mechanism of death and the lymphocyte subsets that are targeted remain unknown. Methods. We extended the characterization of lymphocyte death in a mouse model of ZEBOV infection by evaluating lymphocytes during the course of disease, using flow cytometry, electron microscopy, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). Results. B cell, CD4+ and CD8+ T cell, and NK cell counts all dropped dramatically in the blood of infected BALB/c mice, and lymphocyte death was observed in the spleen by means of TUNEL staining and in the blood by means of electron microscopy. Morphologically, lymphocyte death occurred by both classic apoptosis and apoptosis-like programmed cell death. Conclusions. The early and severe loss of peripheral blood NK and CD8+ lymphocytes in ZEBOV-infected mice is similar to that seen in macaques. The morphological basis of lymphocyte death in ZEBOV-infected mice appears to be both classic apoptosis and apoptosis-like programmed cell death, although lymphocyte apoptosis in ZEBOV-infected nonhuman primates seems to occur primarily via classic apoptosis. The mouse model of ZEBOV infection may be useful for the screening of therapeutics directed against limiting lymphocyte death.

Original languageEnglish (US)
Pages (from-to)S296-S304
JournalJournal of Infectious Diseases
Volume196
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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  • Cite this

    Bradfute, S. B., Braun, D. R., Shamblin, J. D., Geisbert, J. B., Paragas, J., Garrison, A., Hensley, L. E., & Geisbert, T. W. (2007). Lymphocyte death in a mouse model of ebola virus infection. Journal of Infectious Diseases, 196(SUPPL. 2), S296-S304. https://doi.org/10.1086/520602