8ust
In-virion structure of Ebola virus nucleocapsid-like assemblies from recombinant virus-like particles (nucleoprotein, VP24,VP35,VP40)
Structural highlights
FunctionVP24_EBOZM Prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways. Blocks the IFN-induced nuclear accumulation of host phosphorylated STAT1, by interacting with the STAT1-binding region of host importin alpha-1/KPNA1 protein, thereby inhibiting the latter. Without the activity of this protein, activated STAT1 would not enter the nucleus and be unable to activate IFN-induced genes. Plays a role in assembly of viral nucleocapsid and virion budding. May act as a minor matrix protein that plays a role in assembly of viral nucleocapsid and virion budding.[1] [2] [3] [4] Publication Abstract from PubMedFiloviruses, including the 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 the virion. A comparison of intracellular nucleocapsids with prior in-virion nucleocapsid structures reveals that the nucleocapsid further condenses vertically in the virion. The interfaces responsible for nucleocapsid assembly are highly conserved and offer targets for broadly effective antivirals. Intracellular Ebola virus nucleocapsid assembly revealed by in situ cryo-electron tomography.,Watanabe R, Zyla D, Parekh D, Hong C, Jones Y, Schendel SL, Wan W, Castillon G, Saphire EO Cell. 2024 Sep 12:S0092-8674(24)00973-5. doi: 10.1016/j.cell.2024.08.044. PMID:39293445[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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