Structure mapping of dengue and Zika viruses reveals functional long-range interactions View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Roland G. Huber, Xin Ni Lim, Wy Ching Ng, Adelene Y. L. Sim, Hui Xian Poh, Yang Shen, Su Ying Lim, Karin B. Sundstrom, Xuyang Sun, Jong Ghut Aw, Horng Khit Too, Peng Hee Boey, Andreas Wilm, Tanu Chawla, Milly M. Choy, Lu Jiang, Paola Florez de Sessions, Xian Jun Loh, Sylvie Alonso, Martin Hibberd, Niranjan Nagarajan, Eng Eong Ooi, Peter J. Bond, October M. Sessions, Yue Wan

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. More... »

PAGES

1408

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09391-8

DOI

http://dx.doi.org/10.1038/s41467-019-09391-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113057240

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30926818


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