In addition to assessing combinatorial contributions of host factors, Drosophila is well suited for examining cooperative interactions between pathogen virulence factors, as presented in the examples above. Many pathogens produce a complex cocktail of virulence factors, subsets of which are often co-expressed from neighboring genes in so-called pathogenicity islands. These coregulated virulence factors are typically delivered by a dedicated injection system and often act by unknown means in various combinations in different host cell types. Such virulence factors from a given pathogenicity island can be expressed in various combinations in specific cell types to identify specific cellular contexts in which they interact. Given the great success of the fly for analyzing the activities of single host or pathogenic factors in disease processes, it will interesting to see whether it also serves as a robust system to study more complex networks of interactions between host pathways or pathogen virulence factors. With the advent of whole genome RNAi tools and comprehensive mutant collections, flies should also provide an important intact model system for identifying unknown activities of virulence factors that act in a multicellular context to inhibit specific signaling systems or to alter contact between neighboring cells in structured tissues and organs. Combined use of Drosophila cells and intact flies in moderate-to high-throughput drug screens is also emerging as an effective strategy to identify compounds, or combinations of existing compounds, that alter the activity of host pathways to counter the effect of pathogens. Clearly, flies have a bright future as tools for further deconstructing human host-pathogen interactions. The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope. Viruses have evolved as genome packaging machines to efficiently transfer nucleic acids between susceptible host cells, ensuring replication. The majority of viruses have hollow, quasispherical shells rather than tubular structures, perhaps because this gives the most efficient packaging of nucleic acid with a fixed copy number of coat protein subunits. In non-enveloped viruses, the volume enclosed by the (usually) icosahedral structure is a constraint on the size of the genome, giving a limited capacity to encode capsid proteins, and usually restricts the genome copy number, or ploidy of the virion, to one [1] . Most membraneenveloped viruses are also quasi-spherical, but their symmetry is frequently less well-ordered, which is usually described as pleomorphic. This feature allows some flexibility in volume, which could accommodate variation in the size of the genome or its copy number. Nevertheless, most viruses, irrespective of their architecture, appear to have evolved to encapsidate only a single copy of their genome within the protein or protein/lipid shell, or a dimeric copy in retroviruses. Notable exceptions are the Paramyxoviridae and the Birnaviridae where particles may contain up to four copies of the RNA genomes [2, 3] . Although some strains of influenza can produce elongated virions, there is a mechanism that selectively encapsidates only one set of genome segments in each virion [4] .