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Open AccessArticle

The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression

1
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany
2
Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany
3
Laboratory of Virology, Division of Intramural Research, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA
*
Author to whom correspondence should be addressed.
Current affiliation: Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.
Current affiliation: Bellingham Technical College, Bellingham, WA 98225, USA.
Cells 2020, 9(1), 187; https://doi.org/10.3390/cells9010187
Received: 20 December 2019 / Revised: 7 January 2020 / Accepted: 9 January 2020 / Published: 11 January 2020
(This article belongs to the Special Issue Cell Biology of Viral Infections)
Ebola virus (EBOV) causes severe outbreaks of viral hemorrhagic fever in humans. While virus-host interactions are promising targets for antivirals, there is only limited knowledge regarding the interactions of EBOV with cellular host factors. Recently, we performed a genome-wide siRNA screen that identified the nuclear RNA export factor 1 (NXF1) as an important host factor for the EBOV life cycle. NXF1 is a major component of the nuclear mRNA export pathway that is usurped by many viruses whose life cycles include nuclear stages. However, the role of NXF1 in the life cycle of EBOV, a virus replicating in cytoplasmic inclusion bodies, remains unknown. In order to better understand the role of NXF1 in the EBOV life cycle, we performed a combination of co-immunoprecipitation and double immunofluorescence assays to characterize the interactions of NXF1 with viral proteins and RNAs. Additionally, using siRNA-mediated knockdown of NXF1 together with functional assays, we analyzed the role of NXF1 in individual aspects of the virus life cycle. With this approach we identified the EBOV nucleoprotein (NP) as a viral interaction partner of NXF1. Further studies revealed that NP interacts with the RNA-binding domain of NXF1 and competes with RNA for this interaction. Co-localization studies showed that RNA binding-deficient, but not wildtype NXF1, accumulates in NP-derived inclusion bodies, and knockdown experiments demonstrated that NXF1 is necessary for viral protein expression, but not for viral RNA synthesis. Finally, our results showed that NXF1 interacts with viral mRNAs, but not with viral genomic RNAs. Based on these results we suggest a model whereby NXF1 is recruited into inclusion bodies to promote the export of viral mRNA:NXF1 complexes from these sites. This would represent a novel function for NXF1 in the life cycle of cytoplasmically replicating viruses, and may provide a basis for new therapeutic approaches against EBOV, and possibly other emerging viruses. View Full-Text
Keywords: Ebola virus; filovirus; inclusion bodies; NXF1; liquid organelles; mRNA export Ebola virus; filovirus; inclusion bodies; NXF1; liquid organelles; mRNA export
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Wendt, L.; Brandt, J.; Bodmer, B.S.; Reiche, S.; Schmidt, M.L.; Traeger, S.; Hoenen, T. The Ebola Virus Nucleoprotein Recruits the Nuclear RNA Export Factor NXF1 into Inclusion Bodies to Facilitate Viral Protein Expression. Cells 2020, 9, 187.

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