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bioRxiv · 10.1101/2023.12.01.569666

Intracellular Ebola Virus nucleocapsid assembly revealed by in situ cryo-electron tomography.

Watanabe, R.·Zyla, D.·Parekh, D.·Hong, C.·Jones, Y.·Schendel, S. L.·Wan, W.·Castillon, G.·Saphire, E. O.
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Abstract

Filoviruses, including Ebola and Marburg viruses, cause hemorrhagic fevers with up to 90% lethality. The viral nucleocapsid is assembled by polymerization of the nucleoprotein (NP) along the viral genome, together with the viral proteins VP24 and VP35. We employed cryo-electron tomography of cells transfected with viral proteins and infected with model Ebola virus, to illuminate assembly intermediates as well as a 9[A] map of the complete intracellular assembly. This structure reveals a previously unresolved, third, and outer layer of NP complexed with VP35. The intrinsically-disordered-region together with the C-terminal domain of this outer layer of NP provides the constant-width between intracellular nucleocapsid bundles and likely functions as a flexible tether to the viral matrix protein in virion. A comparison of intracellular nucleocapsid with prior in-virion nucleocapsid structures reveals the nucleocapsid further condenses vertically in-virion. The interfaces responsible for nucleocapsid assembly are highly conserved and offer targets for broadly effective antivirals.

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Watanabe, R., Zyla, D., Parekh, D., Hong, C., Jones, Y., Schendel, S. L., Wan, W., Castillon, G., Saphire, E. O.. 2023-12-02. Intracellular Ebola Virus nucleocapsid assembly revealed by in situ cryo-electron tomography.. https://doi.org/10.1101/2023.12.01.569666

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