Disruption of Ebola NP 0 VP35 Inclusion Body-like Structures reduce Viral Infection

Viral inclusion bodies (IBs) are potential sites of viral replication and assembly. How viral IBs form remains poorly defined. Here we describe a combined biophysical and cellular approach to identify the components necessary for IB formation during Ebola virus (EBOV) infection. We find that the eNP...

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Bibliographic Details
Published in:Journal of molecular biology 2023-10, Vol.435 (20), p.168241
Main Authors: Wu, Chao, Wagner, Nicole D, Moyle, Austin B, Feng, Annie, Sharma, Nitin, Stubbs, Sarah H, Donahue, Callie, Davey, Robert A, Gross, Michael L, Leung, Daisy W, Amarasinghe, Gaya K
Format: Article
Language:English
Subjects:
Ebolavirus - metabolism
Ebolavirus - physiology
Hemorrhagic Fever, Ebola - virology
Humans
Inclusion Bodies - virology
Nucleoproteins - metabolism
Viral Regulatory and Accessory Proteins - metabolism
Virus Replication
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Summary:Viral inclusion bodies (IBs) are potential sites of viral replication and assembly. How viral IBs form remains poorly defined. Here we describe a combined biophysical and cellular approach to identify the components necessary for IB formation during Ebola virus (EBOV) infection. We find that the eNP VP35 complex containing Ebola nucleoprotein (eNP) and viral protein 35 (eVP35), the functional equivalents of nucleoprotein (N) and phosphoprotein (P) in non-segmented negative strand viruses (NNSVs), phase separates to form inclusion bodies. Phase separation of eNP VP35 is reversible and modulated by ionic strength. The multivalency of eVP35, and not eNP, is also critical for phase separation. Furthermore, overexpression of an eVP35 peptide disrupts eNP VP35 complex formation, leading to reduced frequency of IB formation and limited viral infection. Together, our results show that upon EBOV infection, the eNP VP35 complex forms the minimum unit to drive IB formation and viral replication.
ISSN:1089-8638