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Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation
Abstract
Intracellular cleavage of immature flaviviruses is a critical step in assembly that generates the membrane fusion potential of the E glycoprotein. With cryo–electron microscopy we show that the immature dengue particles undergo a reversible conformational change at low pH that renders them accessible to furin cleavage. At a pH of 6.0, the E proteins are arranged in a herringbone pattern with the pr peptides docked onto the fusion loops, a configuration similar to that of the mature virion. After cleavage, the dissociation of pr is pH-dependent, suggesting that in the acidic environment of the trans-Golgi network pr is retained on the virion to prevent membrane fusion. These results suggest a mechanism by which flaviviruses are processed and stabilized in the host cell secretory pathway.
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Cited by
Dengue virus life cycle: viral and host factors modulating infectivity
Rodenhuis-Zybert, I. A., Wilschut, J., & Smit, J. M. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0357-z · Cited by 499
Recognition determinants of broadly neutralizing human antibodies against dengue viruses
Rouvinski, A., Guardado-Calvo, P., Barba-Spaeth, G., Duquerroy, S., Vaney, M.-C., Kikuti, C. M., Navarro Sanchez, M. E., Dejnirattisai, W., Wongwiwat, W., Haouz, A., et al. (2015) · Nature · doi:10.1038/nature14130 · Cited by 357
A Randomized Controlled Trial of Chloroquine for the Treatment of Dengue in Vietnamese Adults
Tricou, V., Minh, N. N., Van, T. P., Lee, S. J., Farrar, J., Wills, B., Tran, H. T., & Simmons, C. P. (2010) · PLoS Neglected Tropical Diseases · doi:10.1371/journal.pntd.0000785 · Cited by 329
A Physical Interaction Network of Dengue Virus and Human Proteins
Khadka, S., Vangeloff, A. D., Zhang, C., Siddavatam, P., Heaton, N. S., Wang, L., Sengupta, R., Sahasrabudhe, S., Randall, G., Gribskov, M., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.012187 · Cited by 175
Self-citationStructure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy
Bharat, T. A. M., Davey, N. E., Ulbrich, P., Riches, J. D., de Marco, A., Rumlova, M., Sachse, C., Ruml, T., & Briggs, J. A. G. (2012) · Nature · doi:10.1038/nature11169 · Cited by 171
Metadata
- Authors
- Yu, I.-M., Zhang, W., Holdaway, H. A., Li, L., Kostyuchenko, V. A., Chipman, P. R., Kuhn, R. J., Rossmann, M. G., & Chen, J.
- Venue
- Science
- Published
- 2008-03-28
- Volume
- 319
- Issue
- 5871
- Pages
- 1834-1837
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2082809561
- Cited by
- 623
- References
- 0
- FWCI
- 30.07
- Type
- journal article
- Language
- en
- Open access
- closed
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- Yu, I.-M., Zhang, W., Holdaway, H. A., Li, L., Kostyuchenko, V. A., Chipman, P. R., Kuhn, R. J., Rossmann, M. G., & Chen, J. (2008). Structure of the Immature Dengue Virus at Low pH Primes Proteolytic Maturation. Science. https://doi.org/10.1126/science.1153264
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