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| Status |
Public on Sep 01, 2011 |
| Title |
ZEBOV-induced changes in macrophage gene expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. Notably, some cellular interferon-inducible genes were upregulated six hours after exposure to virions and LPS, but not after exposure to VLPVP40-GP. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response.
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| Overall design |
Primary human macrophages from three donors (D1, D2, D3) were harvested at 1 h and 6 h after in vitro exposure to purified Ebola virions and compared to RNA from mock-exposed cells derived from the same donors.
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| Contributor(s) |
Wahl-Jensen V, Kurz S, Feldmann F, Buehler LK, Kindrachuk J, DeFilippis V, da Silva J, Früh K, Kuhn JH, Burton DR, Feldmann H |
| Citation(s) |
22028943 |
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| Submission date |
Aug 30, 2011 |
| Last update date |
Dec 13, 2018 |
| Contact name |
Victor DeFilippis |
| E-mail(s) |
defilipp@ohsu.edu
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| Phone |
503-418-2757
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| Organization name |
Oregon Health and Science University
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| Department |
Vaccine and Gene Therapy Institute
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| Lab |
DeFilippis
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| Street address |
505 NW 185th Ave.
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| City |
Beaverton |
| State/province |
OR |
| ZIP/Postal code |
97006 |
| Country |
USA |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA145321 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31747_RAW.tar |
81.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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