Tracking Ebola virus within host cells

Once a viral genome penetrates a cell's membrane, the host cell is doomed to replicate the alien genome and make the proteins that constitute the virus's coat, or capsid. The capsid proteins self-assemble; the replicated genomes are packed inside; and the newly created viruses burst out of the cell. To reproduce, viruses commandeer the host's molecular factories. But, as a team led by Robert Stahelin of the Indiana University School of Medicine and the University of Notre Dame, Indiana, has discovered, the deadly Ebola virus exploits another, quite different molecule inside cells, actin. Actin polymerizes into filaments that form a cell's internal scaffolding. Its presence in Ebola capsids had been detected before, but its role was unclear. To resolve the mystery, Stahelin and his colleagues created mutant cells whose actin molecules were labeled with mCherry, a red fluorescent protein. They also created mutant Ebola protein, which, when expressed, labeled a capsid protein called VP40 with EGFP, a green fluorescent protein. By using confocal microscopy and single-particle tracking, Stahelin's team found that the actin filaments not only attracted VP40 (see figure), but also directed the proteins' movement through the cell. What's more, by dosing the cells with a toxin that inhibits actin polymerization, the team discovered that actin filaments promote capsid assembly. Given that actin is found in all cells that have nuclei, it's perhaps not surprising that a virus evolved to exploit a ubiquitous molecule. But now that it's been revealed, Ebola's actin dependence could lead to a treatment for the disease, which typically kills 90% of its victims. (E. Adu-Gyamfi et al., Biophys. J. 103, L41, 2012.)—Charles Day