The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever.
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.
Rubins
Kathleen H
KH
Department of Microbiology and Immunology, 299 Campus Dr, Stanford University School of Medicine, Stanford, California 94305, USA. rubins@wi.mit.edu
Hensley
Lisa E
LE
Wahl-Jensen
Victoria
V
Daddario DiCaprio
Kathleen M
KM
Young
Howard A
HA
Reed
Douglas S
DS
Jahrling
Peter B
PB
Brown
Patrick O
PO
Relman
David A
DA
Geisbert
Thomas W
TW
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
D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus; D005337:Fibrin; D007372:Interferons; D051722:ADAM Proteins; D000072198:ADAM17 Protein