Open Access Research

The temporal program of peripheral blood gene expression in the response of nonhuman primates to Ebola hemorrhagic fever

Kathleen H Rubins123*, Lisa E Hensley4, Victoria Wahl-Jensen4, Kathleen M Daddario DiCaprio4, Howard A Young5, Douglas S Reed4, Peter B Jahrling4, Patrick O Brown26, David A Relman178 and Thomas W Geisbert4

Author Affiliations

1 Department of Microbiology and Immunology, 299 Campus Dr., Stanford University School of Medicine, Stanford, California 94305, USA

2 Department of Biochemistry, 279 Campus Dr., Stanford University School of Medicine, Stanford, California 94305, USA

3 Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA

4 US Army Medical Research Institute of Infectious Diseases, 1425 Porter St., Fort Detrick, Maryland 21702-5011, USA

5 National Cancer Institute - Frederick, 1050 Boyles St., Frederick, Maryland 21702, USA

6 Howard Hughes Medical Institute, 279 Campus Dr., Stanford University School of Medicine, Stanford, California 94305, USA

7 Department of Medicine, 300 Pasteur Dr., Stanford University School of Medicine, Stanford, California 94305, USA

8 Veterans Affairs Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, California 94304, USA

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Genome Biology 2007, 8:R174  doi:10.1186/gb-2007-8-8-r174

Published: 28 August 2007

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-α converting enzyme (TACE)/α-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.

Conclusion

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.