Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus

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

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Abstract

Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) CCAAT/enhancer-binding protein alpha, (2) tumor protein 53, and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection.

Original languageEnglish (US)
Article numbere3061
JournalPLoS neglected tropical diseases
Volume8
Issue number7
DOIs
StatePublished - Jul 2014

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ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Garamszegi, S., Yen, J. Y., Honko, A. N., Geisbert, J. B., Rubins, K. H., Geisbert, T. W., Xia, Y., Hensley, L. E., & Connor, J. H. (2014). Transcriptional Correlates of Disease Outcome in Anticoagulant-Treated Non-Human Primates Infected with Ebolavirus. PLoS neglected tropical diseases, 8(7), [e3061]. https://doi.org/10.1371/journal.pntd.0003061