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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.
DOI: 10.1038/s41467-019-09391-8
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
Fulltext Permission: open
Fulltext Availability: With Fulltext
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