Schematic representation of the biogenesis of RV replication complexes. Schematic representation of the biogenesis of RV replication complexes. Step 1, The RV virion attaches to the cell surface and is translocated to the coated pit. Step 2, The coated pit then pinches off to form a coated vesicle that contains the virion. Step 3, The virion passes through a series of endosomes with progressively acidic pH until it arrives at an endosome where the environment is sufficiently acidic to trigger the uncoating process. The E1 and capsid proteins undergo conformational changes that result in the release of the viral genomic RNA into the cytoplasm. Step 4, Release of the viral RNA triggers the transformation of the endosome, and vesicles are induced to form within the endosome. This leads to the formation of the replication complex. Concomitantly, the RER migrates to the vicinity of the virus-modified endosome. At this early stage of the infection, the RER is associated with the side of the vacuole where the vesicles are located. Step 5, As infection progresses, the RER surrounds the entire vacuole, which is lined internally with vesicles. While these events are occurring, the virus-modified endosome fuses to a lysosome as part of its life cycle. Step 6, The replication complex continues in its life cycle as a virus-modified lysosome and eventually expels its lysosomal contents, including the vesicles, after fusion of the lysosomal vacuole membrane to the plasma membrane. Jia-Yee Lee, and D. Scott Bowden Clin. Microbiol. Rev. 2000; doi:10.1128/CMR.13.4.571