Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus

PLoS Negl Trop Dis. 2014 Jul 31;8(7):e3061. doi: 10.1371/journal.pntd.0003061. eCollection 2014.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anticoagulants / therapeutic use*
  • Disease Models, Animal
  • Ebolavirus / pathogenicity*
  • Gene Expression Profiling*
  • Hemorrhagic Fever, Ebola / immunology
  • Hemorrhagic Fever, Ebola / pathology*
  • Host-Pathogen Interactions*
  • Leukocytes, Mononuclear / immunology
  • Macaca mulatta
  • Microarray Analysis
  • Treatment Outcome

Substances

  • Anticoagulants