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Title: | Structure mapping of dengue and Zika viruses reveals functional long-range interactions | Authors: | Huber, Roland G. Lim, Xin Ni Ng, Wy Ching Sim, Adelene Y. L. Poh, Hui Xian Shen, Yang Lim, Su Ying Sundstrom, Karin B. Sun, Xuyang Aw, Jong Ghut Too, Horng Khit Boey, Peng Hee Wilm, Andreas Chawla, Tanu Choy, Milly M. Jiang, Lu de Sessions, Paola Florez Loh, Xian Jun Alonso, Sylvie Hibberd, Martin Nagarajan, Niranjan Ooi, Eng Eong Bond, Peter J. Sessions, October M. Wan, Yue |
Keywords: | Zika Virus Science::Biological sciences Dengue Virus |
Issue Date: | 2019 | Source: | Huber, R. G., Lim, X. N., Ng, W. C., Sim, A. Y. L., Poh, H. X., Shen, Y., . . . Wan, Y. (2019). Structure mapping of dengue and Zika viruses reveals functional long-range interactions. Nature Communications, 10(1), 1408-. doi:10.1038/s41467-019-09391-8 | Series/Report no.: | Nature Communications | Abstract: | Dengue (DENV) and Zika (ZIKV) viruses are clinically important members of the Flaviviridae family with an 11 kb positive strand RNA genome that folds to enable virus function. Here, we perform structure and interaction mapping on four DENV and ZIKV strains inside virions and in infected cells. Comparative analysis of SHAPE reactivities across serotypes nominates potentially functional regions that are highly structured, conserved, and contain low synonymous mutation rates. Interaction mapping by SPLASH identifies many pair-wise interactions, 40% of which form alternative structures, suggesting extensive structural heterogeneity. Analysis of shared interactions between serotypes reveals a conserved macro-organization whereby interactions can be preserved at physical locations beyond sequence identities. We further observe that longer-range interactions are preferentially disrupted inside cells, and show the importance of new interactions in virus fitness. These findings deepen our understanding of Flavivirus genome organization and serve as a resource for designing therapeutics in targeting RNA viruses. | URI: | https://hdl.handle.net/10356/87105 http://hdl.handle.net/10220/49868 |
DOI: | 10.1038/s41467-019-09391-8 | Schools: | School of Biological Sciences | Rights: | © 2019 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
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