Doñate-Macián, PauJungfleisch, Jennifer, 1986-Pérez Vilaró, Gemma, 1985-Rubio Moscardó, FannyPerálvarez Marín, AlexDíez Antón, Juana, 1962-Valverde, M. A. (Miguel Ángel), 1963-2018-06-212018-06-212018Doñate-Macián P, Jungfleisch J, Pérez-Vilaró G, Rubio-Moscardo F, Perálvarez-Marín A, Diez J et al. The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity. Nat Commun. 2018 Jun 13;9(1):2307. DOI: 10.1038/s41467-018-04776-72041-1723http://hdl.handle.net/10230/34947Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity.application/pdfeng© The Author(s) 2018. 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-018-04776-7Ion channel signallingViral infectioninfo:eu-repo/semantics/openAccess