Abstract

Protein-protein interactions play central roles in the molecular conflict between viruses and their hosts. RNA , another key biological macromolecule, has an inherent capacity to form structures and specific interactions through base-complementarity. However, the prevalence and roles of host-pathogen RNA -RNA interactions remain largely unreachable due to technological limitations. I have recently developed COMRADES , a scalable method for studying dynamic RNA structures and RNA -RNA interactions inside cells, providing high-throughput conformation capture (Hi-C) capabilities to RNA biology. Applying COMRADES to Zika virus inside human and mosquito cells revealed the first-ever structure of a wildtype viral RNA genome inside its host cell, demonstrating an unanticipated level of structural-dynamics. I identified strong evidence for replication-coupled cyclisation of viral RNA genomes, and for multiple site-specific interactions between the viral genome and human noncoding RNAs. I discovered a triple-function element in the viral RNA genome involved in translation, replication, and binding to human microRNA-21. The newly identified structures and interactions uncover a rich and little explored universe of RNA -based communication pathways between cells and their pathogens, which can be harnessed for the design of new antiviral strategies.