Profiling of Secretory mRNAs in Dengue Virus Infection: Possible Implications in Thrombocytopenia

Dengue virus is a global health concern resulting in approximately 100 million infections and 21 000 deaths annually. The disease progresses from dengue without warning signs (PLAN A) to dengue with warning signs (PLAN B) and then to severe dengue (PLAN C). However, the molecular mechanisms underlying this transition are not known. In the absence of effective antivirals and vaccines, predicting disease severity early is the only option for better disease management. Extracellular vesicles (EVs) are membrane-bound vesicles secreted from cells and contain miRNA, proteins, and mRNA, which play a crucial role in cell-to-cell communication. Our work involves identifying and characterizing the mRNAs in the EVs isolated from patients in different stages of dengue severity, i.e., PLAN A, PLAN B, and PLAN C. The pathway analysis of these mRNAs enriched in EVs revealed that they play crucial roles in cytokine and chemokine signaling and platelet degranulation, all of which are known to be dysregulated as dengue progresses to severe disease. Further validations using patient samples showed that the selective secretion of these mRNAs from platelets may affect platelet functions. Overall, our study is the first to show the full secretory mRNA profile across different stages of dengue disease severity and reveals a novel mechanism by which the selective secretion of specific mRNAs upon infection may dysregulate host immune responses and contribute to thrombocytopenia, thereby exacerbating disease severity.