UC San Diego

Asp-Glu-Ala-Asp (DEAD) box helicase 3 X-Linked (DDX3X) displays important functions in promoting cellular processes, such as RNA binding, transcriptional regulation, RNA export, and translation initiation, through providing nucleation centers for larger RNA-protein complexes. The Zuniga lab previously showed that DDX3X has a pro-viral role and also suppresses type-I interferon (IFN-I) during Lymphocytic choriomeningitis Virus (LCMV) infection in A549, a lung cancer cell line. Therefore, DDX3X is a promising target for both LCMV control and IFN-I regulation and understanding the mechanism behind these functions is key. Recently, the Zuniga lab aimed to extend these findings to primary human fibroblasts. We generated DDX3X deficient Normal Human Dermal Fibroblasts (NHDF) and assessed their IFN-I production and viral levels upon LCMV infection, addressing a gap of knowledge in the clinical translatability of DDX3X as a drug target. To unwind the mechanism behind the pro-viral role and IFN-I suppressing function, we examined the potential change in localization of DDX3X during infection. We stained for DDX3X in both uninfected and infected A549 and NHDF and visualized the fluorescence signals under confocal microscopy. We found that the DDX3X signal intensity at both the nucleus and whole cell level is altered upon LCMV infection in a cell type-dependent manner, but LCMV does not seem to induce nuclear shuttling. Together my work helped to extend the pro-viral and IFN-I suppression roles of DDX3X, as well as informed on DDX3X cellular localization after infection.