(A) Cellular VPS pathway and MVB biogenesis. Receptors on the plasma membrane destined for degradation (e.g. transferrin receptors) are internalized into vesicles by endocytosis which fuse with other vesicles to form endosomes en route to the lysosome. Ubiquitination of cargo proteins recruits the ESCRT complexes. To form MVBs, Vps4 AAA-ATPase activity is required to remove ESCRT-III proteins from the membrane and induce vesicularization. (B) Enveloped virus budding from the plasma membrane. For some enveloped viruses, viral proteins recruit components of the ESCRT complex through L domains, redirecting the MVB formation machinery from endosomes to sites of virus budding. (C) Abscission. To complete cytokinesis, abscission requires the recruitment of ESCRT proteins Tsg101 and AIP1/Alix by Cep55 to the midbody, and the activity of Vps4. The membrane topology of abscission, when the daughter cell pinches off, is equivalent to both MVB formation and virus budding.