Principal investigator: Juana Díez
Because of their genetic simplicity, viruses completely depend on the cellular machinery for expansion. The identification of crucial virus-cell interactions is thus essential to understand virus biology. In addition, these studies may provide novel strategies for therapeutic interventions and uncover new mechanisms to regulate gene expression used not only by viruses but also by the host. In fact, most cellular post-transcriptional processes have been uncovered through viral studies.
Positive-strand RNA ((+)RNA) viruses include major human pathogens such as the Hepatitis C virus (HCV) and the emerging Denguevirus (DENV) and Chikungunya virus (CHIKV). Upon entry into the cell, a crucial common step in (+)RNA virus life cycle is the translation of their genomes. How do they manage to efficiently compete with thousands of cellular mRNAs? How do they change the translational environment of their host to their benefit? Intriguingly, we have shown that (+)RNA viruses hijack cellular mRNA degradation proteins to translate their genomes. Now we aim to analyze this unexpected role of mRNA degradation proteins in translation enhancement and to decipher viral and host mRNA translation landscapes throughout infection. For this we will combine biochemical, cell culture and in vivo studies, and novel systems biology approaches. As experimental systems we use the infection of HCV, CHIKV and DENV in human cell lines, and the replication of the brome mosaic virus in yeast, a well established model system to study fundamental aspects of (+)RNA biology in a relatively simple genetic background. We expect that the obtained results will lead to fundamental new insights into the interface between cellular translational control and viral RNA expansion.