Filovirus Tropism: Cellular Molecules for Viral Entry

Takada, Ayato

In the early years, studies of filoviruses were hampered by its extraordinary pathogenicity, which requires biosafety level 4 containment. To circumvent this problem, pseudotype virus systems for functional analysis of filovirus GPs have been established (Takada et al., 1997; Wool-Lewis and Bates, 1998) . The systems rely on recombinant viruses (e.g., replication-competent or -incompetent vesicular stomatitis virus and retroviruses) that contain filovirus GP instead of their own GPs (Figure 5 ). Such pseudotype virus systems enable us to investigate cell tropism mediated by simple interaction between filovirus GP and its cellular ligands. Using such a system, it was shown that pseudotyped viruses infected primate cells more efficiently than any of the other mammalian or avian cells examined, in a manner consistent with the host range tropism of Ebola virus, and that cell-surface GPs with N-linked oligosaccharide chains might contribute to the entry of Ebola viruses, presumably acting as a specific receptor and/or cofactor for virus entry (Takada et al., 1997) . Furthermore, filovirus receptor-deficient cell lines that have been used in expression cloning strategies searching for filovirus entry mediators were discovered in an early study (Wool-Lewis and Bates, 1998) . Thus, Frontiers in Microbiology | Virology FIGURE 2 | Structure of Ebola virus particle and genome organization. Electron micrograph of Ebola virus particle (A), its diagram (B), and negative-sense genome organization (C) are shown. Viral protein names and functions are described in the text. Transcribing the glycoprotein (GP) gene produces a soluble GP (sGP). Transcriptional editing accompanied by frame shifting is required to produce full-length, membrane-anchored GP, which shares its first 295 amino acid residues with sGP. pseudotype virus systems are an essential tool for recent filovirus receptor research.