title: The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever.
abstract: BACKGROUND
  Infection with Ebola virus (EBOV) causes a fulminant and often fatal hemorrhagic fever. In order to improve our understanding of EBOV pathogenesis and EBOV-host interactions, we examined the molecular features of EBOV infection in vivo.
  
  
  RESULTS
  Using high-density cDNA microarrays, we analyzed genome-wide host expression patterns in sequential blood samples from nonhuman primates infected with EBOV. The temporal program of gene expression was strikingly similar between animals. Of particular interest were features of the data that reflect the interferon response, cytokine signaling, and apoptosis. Transcript levels for tumor necrosis factor-alpha converting enzyme (TACE)/alpha-disintegrin and metalloproteinase (ADAM)-17 increased during days 4 to 6 after infection. In addition, the serum concentration of cleaved Ebola glycoprotein (GP2 delta) was elevated in late-stage EBOV infected animals. Of note, we were able to detect changes in gene expression of more than 300 genes before symptoms appeared.
  
  
  CONCLUSIONS
  These results provide the first genome-wide ex vivo analysis of the host response to systemic filovirus infection and disease. These data may elucidate mechanisms of viral pathogenesis and host defense, and may suggest targets for diagnostic and therapeutic development.
authors.affiliation: Department of Microbiology and Immunology, 299 Campus Dr, Stanford University School of Medicine, Stanford, California 94305, USA. rubins@wi.mit.edu
authors.forename: Kathleen H
authors.initials: KH
authors.lastname: Rubins
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.forename: Victoria
authors.initials: V
authors.lastname: Wahl-Jensen
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Daddario DiCaprio
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Reed
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Brown
authors.forename: David A
authors.initials: DA
authors.lastname: Relman
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
mesh_terms: D051722:ADAM Proteins / Q000235:genetics; D000072198:ADAM17 Protein; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D005337:Fibrin / Q000378:metabolism; D020869:Gene Expression Profiling; D019142:Hemorrhagic Fever, Ebola / Q000097:blood* / Q000235:genetics*; D007113:Immunity, Innate / Q000235:genetics; D007372:Interferons / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008252:Macaca fascicularis; D020411:Oligonucleotide Array Sequence Analysis; D014759:Viral Envelope Proteins / Q000097:blood / Q000378:metabolism
chemical_list: D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D005337:Fibrin; D007372:Interferons; D051722:ADAM Proteins; D000072198:ADAM17 Protein