The ESCRT pathway and HIV-1 budding: A paradigm of viral exploitation of cellular regulation.

The ESCRT (Endosomal Sorting Complexes Required for Transport) pathway is a conserved cellular machinery essential for reverse-topology membrane fission events, such as multivesicular body biogenesis and cytokinesis. Human Immunodeficiency Virus Type 1 (HIV-1) co-opts this machinery to mediate the final scission step of virion budding from the host cell membrane. This review presents our current understanding of how HIV-1 hijacks the ESCRT system, moving beyond a simple recruitment model to a dynamic interplay with host cell regulation. We explore the spatial organization of the budding machinery at nanoscale domains, the layered control systems governing ESCRT activity, including molecular switches, post-translational modifications, and host restriction factors, and the integration of viral budding with cellular signaling networks. A key emerging theme is the plasticity of the viral budding program, where redundant recruitment pathways and adaptive sequence variations allow HIV-1 to maintain release across diverse cell types and under immune pressure. Finally, we discuss the translational implications of these insights, evaluating the ESCRT pathway as a source of potential therapeutic targets and outlining the challenges and future directions for exploiting this essential host-virus interface.