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Molecular insights into nucleocapsid assembly and transport in Marburg and Ebola viruses
Open accessPreprint — published as 10.1128/mbio.01557-25 · Paper page
Abstract
Live-cell imaging enables visualization of the spatiotemporal dynamics of signals in cells. The intracytoplasmic movement of nucleocapsids is crucial during the lifecycle of enveloped viruses, but the molecular mechanisms governing their assembly and transport are not fully understood. Using a MARV live-cell imaging system, we identified three nucleocapsid proteins—NP, VP35, and VP24—that are necessary and sufficient to form transport-competent nucleocapsid-like structures (NCLSs). These findings are consistent with observations in Ebola virus (EBOV). Interestingly, despite incompatibility among these proteins, VP30 interacts with nucleocapsid proteins from both MARV and EBOV, supporting viral transcription and replication in heterologous systems. Furthermore, we show that the conserved PPxPxY motif at the C-terminus of NP regulates NP−VP30 interactions in both homologous and heterologous contexts, and is crucial for VP30 association with NCLSs. Because this motif is conserved across filoviruses, it represents a promising target for antiviral development. Our findings advance the understanding of nucleocapsid formation and offer new avenues for therapeutic intervention against MARV and EBOV.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Takamatsu, Y., Dolnik, O., Hirabayashi, A., Okamoto, K., Kurashige, T., Shangfan, H., Harumi, C. O., & Noda, T.
- Affiliations
- Nagasaki University (JP)
- Philipps University of Marburg (DE)
- Kyoto University (JP)
- Uppsala University (SE)
- Department of Virology, Institute of Tropical Medicine, Nagasaki University (ITM-NU), Japan
- Corresponding author
- Takamatsu, Yuki
- Venue
- mBio
- Publisher
- openRxiv
- Published
- 2025-05-13
- Volume
- 16
- Issue
- 11
- Pages
- e0155725-e0155725
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC12607913
- OpenAlex
- W4414410146
- Cited by
- 0
- References
- 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Institutional Repositories DataBase (IRDB) (submittedVersion, other-oa)
- Funders
- Takeda Science Foundation
- Asahi Glass Foundation
- Philipps-Universität Marburg
- Japan Agency for Medical Research and Development (JP22fm0208101, 24fm0208101j0008, JP24fm0208101, JP23fk0108656, 22KK0115, JP223fa627004 JP24fm0208101 JP23fm0208101 JP22fm0208101 JP23fk0108656 JP23wm0125006 JP22wm0325, 24fm0208101j0008 JP23fm0208101 and 22fk0108552h0001, JP223fa627004, JP23fm0208101)
- Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care
- Kurozumi Medical Foundation
- Terumo Foundation for Life Sciences and Arts
- NOVARTIS Foundation (Japan) for the Promotion of Science
- MSD Life Science Foundation, Public Interest Incorporated Foundation
- Japan Society for the Promotion of Science (19K16666, 22K19431, 18J01631, JPJSCCA20190008, 18J01631 19K16666 and 21K07059 22KK0115, 21K07059, 22KK0115)
- Institute of Medical Science, University of Tokyo
- Topics
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Keywords
- nucleocapsid assembly, Marburg virus, Ebola virus, filoviruses, nucleocapsid protein, VP30, VP35, VP24, viral transcription and replication, antiviral drug targets, live-cell imaging
- MeSH terms
- Animals, Cell Line, Humans, Nucleoproteins, Protein Binding, Transcription Factors, Viral Proteins, Virus Replication, Virus Assembly, Nucleocapsid, Nucleocapsid Proteins, Marburgvirus, Ebolavirus
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