The article investigates the composition and three-dimensional architecture of the replication and assembly sites of the dengue virus (DENV). Using electron microscopy, the authors find that DENV-induced vesicles, convoluted membranes, and virus particles are derived from the endoplasmic reticulum (ER). Double-stranded RNA, a marker of RNA replication, is detected inside these vesicles. Electron tomography reveals that DENV-induced membrane structures form a continuous network derived from the ER. The study also identifies pores in the vesicles that may facilitate the release of newly synthesized viral RNA and the budding of virus particles on ER membranes. These findings provide insights into the coordination of distinct steps in the flavivirus replication cycle and suggest that DENV modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus.The article investigates the composition and three-dimensional architecture of the replication and assembly sites of the dengue virus (DENV). Using electron microscopy, the authors find that DENV-induced vesicles, convoluted membranes, and virus particles are derived from the endoplasmic reticulum (ER). Double-stranded RNA, a marker of RNA replication, is detected inside these vesicles. Electron tomography reveals that DENV-induced membrane structures form a continuous network derived from the ER. The study also identifies pores in the vesicles that may facilitate the release of newly synthesized viral RNA and the budding of virus particles on ER membranes. These findings provide insights into the coordination of distinct steps in the flavivirus replication cycle and suggest that DENV modifies ER membrane structure to promote replication and efficient encapsidation of the genome into progeny virus.