Ebola virion attachment and entry into human macrophages profoundly effects early cellular gene expression.

Authors:
Wahl-Jensen V, Kurz S, Feldmann F, Buehler LK, Kindrachuk J, DeFilippis V, da Silva Correia J, Früh K, Kuhn JH, Burton DR, Feldmann H.
In:
Source: Other
Publication Date: (2011)
Issue: 5(10): ePub
Research Area:
Basic Research
Cells used in publication:
Vero
Species: monkey
Tissue Origin: kidney
Monocyte, human
Species: human
Tissue Origin: blood
Macrophage, human
Species: human
Tissue Origin: blood
293T
Species: human
Tissue Origin: kidney
Culture Media:
Experiment
The author obtained monocytes from Lonza and differentiated the monocytes into macrophages by culturing the cells in RPMI + 20% FBS. After differentiation, the cells were then infected with ebola and monitored for transcriptional changes. The author noted significant changes in mRNA concentrations encoding for 88 cellular proteins.
Abstract
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 (GP(1,2)) 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 GP(1,2) (VLP(VP40-GP)) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLP(VP40) (particles lacking GP(1,2)) caused an aberrant response. This suggests that GP(1,2) binding to macrophages plays an important role in the immediate cellular response.