title: Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus.
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.
authors: Bioinformatics Program, Boston University, Boston, Massachusetts, University of America.
authors: Sara
authors: S
authors: Garamszegi
authors: Department of Microbiology, School of Medicine, Boston University, Boston, Massachusetts, University of America; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, University of America.
authors: Judy Y
authors: JY
authors: Yen
authors: U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America.
authors: Anna N
authors: AN
authors: Honko
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Joan B
authors: JB
authors: Geisbert
authors: National Aeronautics and Space Administration, Houston, Texas, United States of America.
authors: Kathleen H
authors: KH
authors: Rubins
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors: Thomas W
authors: TW
authors: Geisbert
authors: Bioinformatics Program, Boston University, Boston, Massachusetts, University of America; Department of Bioengineering, McGill University, Montreal, Canada.
authors: Yu
authors: Y
authors: Xia
authors: Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, United States of America.
authors: Lisa E
authors: LE
authors: Hensley
authors: Bioinformatics Program, Boston University, Boston, Massachusetts, University of America; Department of Microbiology, School of Medicine, Boston University, Boston, Massachusetts, University of America; National Emerging Infectious Diseases Laboratories, Boston University, Boston, Massachusetts, University of America.
authors: John H
authors: JH
authors: Connor
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000472:pathogenicity*; D020869:Gene Expression Profiling; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000473:pathology*; D054884:Host-Pathogen Interactions; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D046228:Microarray Analysis; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants