Megakaryocytic Differentiation Regulates the Permissiveness and Antiviral Response of the Megakaryocytic Erythroid Progenitor to Dengue Virus

Dengue virus (DENV) affects not only peripheral immune cells but also hematopoietic progenitors in the bone marrow, particularly megakaryocytic precursors, which contribute to the thrombocytopenia characteristic of the disease. In this study, we evaluated the relationship between the differentiation status of the megakaryocytic lineage and its permissiveness and antiviral response to DENV. Our results demonstrate that the erythroid-megakaryocytic precursor (K562 cells) was more permissive to DENV infection than megakaryoblasts, as evidenced by immunofluorescence, flow cytometry, and quantification of viral particles. The antiviral response in K562 cells peaked at three days post-infection, with maximal expression of genes associated with the type I interferon (IFN-I) pathway. In vitro-induced differentiation of K562 cells reduced the initial susceptibility to DENV and enhanced the expression of Toll-like receptor 3 (TLR3) and the type I interferon receptor (IFNAR1), accelerating and intensifying IFN-β secretion, and increasing the expression of OAS2 and IRF3. Furthermore, pretreatment of K562 cells with recombinant IFN-β significantly reduced viral replication from the first day post-infection. Collectively, these findings demonstrate for the first time that the differentiation status of erythroid-megakaryocytic progenitor critically shapes their antiviral response and underscore the central role of IFN-β in the early restriction of DENV infection.