Identification of an ion channel used by viruses to infect cells
Identification of an ion channel used by viruses to infect cells.
Doñate-Macian P. Jungfleisch J., Pérez-Vilaró G., Rubio-Moscardo F., Perálvarez-Marín A., Diez J. and , Valverde M.A. The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity. Nature Communications (2018) 9:2307; DOI: 10.1038/s41467-018-04776-7.
Abstract
Ion 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.
The Dengue virus and mosquito. Credit: Paul Young and Daniel Watterson, University of Queensland.