Therapeutics of Ebola hemorrhagic fever: Whole-genome transcriptional analysis of successful disease mitigation

Judy Y. Yen, Sara Garamszegi, Joan B. Geisbert, Kathleen H. Rubins, Thomas Geisbert, Anna Honko, Yu Xia, John H. Connor, Lisa E. Hensley

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28 Scopus citations

Abstract

The mechanisms of Ebola (EBOV) pathogenesis are only partially understood, but the dysregulation of normal host immune responses (including destruction of lymphocytes, increases in circulating cytokine levels, and development of coagulation abnormalities) is thought to play a major role. Accumulating evidence suggests that much of the observed pathology is not the direct result of virus-induced structural damage but rather is due to the release of soluble immune mediators from EBOV-infected cells. It is therefore essential to understand how the candidate therapeutic may be interrupting the disease process and/or targeting the infectious agent. To identify genetic signatures that are correlates of protection, we used a DNA microarray-based approach to compare the host genome-wide responses of EBOV-infected nonhuman primates (NHPs) responding to candidate therapeutics. We observed that, although the overall circulating immune response was similar in the presence and absence of coagulation inhibitors, surviving NHPs clustered together. Noticeable differences in coagulation-associated genes appeared to correlate with survival, which revealed a subset of distinctly differentially expressed genes, including chemokine ligand 8 (CCL8/MCP-2), that may provide possible targets for early-stage diagnostics or future therapeutics. These analyses will assist us in understanding the pathogenic mechanisms of EBOV infection and in identifying improved therapeutic strategies.

Original languageEnglish (US)
JournalJournal of Infectious Diseases
Volume204
Issue numberSUPPL. 3
DOIs
StatePublished - Nov 1 2011

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ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Yen, J. Y., Garamszegi, S., Geisbert, J. B., Rubins, K. H., Geisbert, T., Honko, A., Xia, Y., Connor, J. H., & Hensley, L. E. (2011). Therapeutics of Ebola hemorrhagic fever: Whole-genome transcriptional analysis of successful disease mitigation. Journal of Infectious Diseases, 204(SUPPL. 3). https://doi.org/10.1093/infdis/jir345