Taking together, our data indicate that the immediate responses of early cellular ZEBOV targets in the human organism derive from virion binding/entry mediated by the ZEBOV spike glycoprotein and do not require virus gene expression. The fact that many surveyed genes responded similarly to VLP VP40-GP , but not to VLP VP40 , treatment clearly supports this notion. However, the fact that some genes, such as those encoding TF or skin collagenase, were triggered only by Ebola virions but not VLP VP40-GP or LPS indicate that these genes must be influenced by factors other than virus binding or entry, such as other components packaged within Ebola virions in addition to GP 1,2 and VP40. In this regard, it is important to remember that infectious Ebola virions not only consist of seven structural proteins (NP, VP35, VP40, GP 1,2 , VP30, VP24, and L) but also contain cellular transmembrane proteins that are usurped by budding virions [52] . Figure S1 MA plot depicting the overall distribution of gene expression changes as a function of average signal intensity for human macrophages obtained from three different donors. Each data set compares gene expression levels Figure 6 . Determination of relative changes in expression levels of 21 cellular genes in primary human macrophages. Depicted are fold-changes at the 1 h and 6 h time points after exposure to Ebola virions compared to mock-exposed cells, cells exposed to purified Ebola virionlike particles (VLPs) containing VP40 and GP 1,2 (VLP VP40-GP ) or VLPs containing VP40 only (VLP VP40 ), or cells treated with mock-VLP preparation. As controls, macrophages of each donor were treated in parallel with latex beads or with 10 ng of LPS. and changes in primary macrophages exposed to Ebola virions compared to mock-exposure at 1 h (A) and 6 h (B). (TIF)