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

Details

• Alternative Title:
  PLoS Negl Trop Dis
• Personal Author:
  Garamszegi, Sara ; Yen, Judy Y. ; Honko, Anna N. ; Geisbert, Joan B. ; Rubins, Kathleen H. ; Geisbert, Thomas W. ; Xia, Yu ; Hensley, Lisa E. ; Connor, John H.
• Description:
  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.
• Subjects:
  Animals Anticoagulants Disease Models, Animal Ebolavirus Gene Expression Profiling Hemorrhagic Fever, Ebola Host-Pathogen Interactions Leukocytes, Mononuclear Macaca Mulatta Microarray Analysis Treatment Outcome

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• Source:
  PLoS Negl Trop Dis. 2014; 8(7).
• Document Type:
  Journal Article
• Volume:
  8
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:c8548e66c8bd267622ff55cfaa48ba46c736fa8127cf4bcc9bdb9178164e7d5c
• Download URL:
  https://stacks.cdc.gov/view/cdc/24808/cdc_24808_DS1.pdf
• File Type:
  [PDF - 1.05 MB ]