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Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication
Open accessAbstract
SUMMARY Many RNA viruses remodel intracellular membranes to generate specialized sites for RNA replication. How membranes are remodeled and what properties make them conducive for replication are unknown. Here we show how RNA viruses can manipulate multiple components of the cellular secretory pathway to generate organelles specialized for replication that are distinct in protein and lipid composition from the host cell. Specific viral proteins modulate effector recruitment by Arf1 GTPase and its guanine nucleotide exchange factor GBF1, promoting preferential recruitment of phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) to membranes over coat proteins, yielding uncoated phosphatidylinositol-4-phosphate (PI4P) lipid-enriched organelles. The PI4P-rich lipid micro-environment is essential for both enteroviral and flaviviral RNA replication; PI4KIIIβ inhibition interferes with this process; and enteroviral RNA polymerases specifically bind PI4P. These findings reveal how RNA viruses can selectively exploit specific elements of the host to form specialized organelles where cellular phosphoinositide lipids are key to regulating viral RNA replication.
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Cited by
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Blomen, V. A., Májek, P., Jae, L. T., Bigenzahn, J. W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F. R., Olk, N., Stukalov, A., et al. (2015) · Science · doi:10.1126/science.aac7557 · Cited by 857
Heaton, N. S., Perera, R., Berger, K. L., Khadka, S., LaCount, D. J., Kuhn, R. J., & Randall, G. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010811107 · Cited by 566
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Robinson, S. M., Tsueng, G., Sin, J., Mangale, V., Rahawi, S., McIntyre, L. L., Williams, W., Kha, N., Cruz, C., Hancock, B. M., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004045 · Cited by 322
Metadata
- Authors
- Hsu, N.-Y., Ilnytska, O., Belov, G., Santiana, M., Chen, Y.-H., Takvorian, P. M., Pau, C., van der Schaar, H., Kaushik-Basu, N., Balla, T., Cameron, C. E., Ehrenfeld, E., van Kuppeveld, F. J. M., & Altan-Bonnet, N.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 141
- Issue
- 5
- Pages
- 799-811
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2123799993
- Cited by
- 682
- References
- 0
- FWCI
- 17.85
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hsu, N.-Y., Ilnytska, O., Belov, G., Santiana, M., Chen, Y.-H., Takvorian, P. M., Pau, C., van der Schaar, H., Kaushik-Basu, N., Balla, T., Cameron, C. E., Ehrenfeld, E., van Kuppeveld, F. J. M., & Altan-Bonnet, N. (2010). Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication. Cell. https://doi.org/10.1016/j.cell.2010.03.050
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