2025 Volume 65 Issue 6 Pages 310-314
Filoviruses like Ebola and Marburg cause lethal hemorrhagic fevers. The nucleocapsid (NC) forms through nucleoprotein (NP) polymerization along the genome with VP24 and VP35. Using cryo-electron tomography, we reveal the first in-cell complete NC structure at 9 Å resolution and identify the previously unknown 3rd NC layer composed of the NP-VP35 complex. This NP’s C-terminal region maintains spacing between NC bundles in cells and is linked to the viral matrix protein in the virion. Comparing in-cell and in-virion NCs shows further condensation in the virions. The assembly interfaces of NC identified here are highly conserved among all five pathogenic filoviruses, offering promising targets for broad-spectrum antivirals.
