The Human Immunodeficiency Virus Type 1 Budding Machinery: Deconstructing the Endosomal Sorting Complexes Required...

The final step of the Human immunodeficiency virus type 1 (HIV-1) replication cycle, virion budding and scission from the host cell membrane, is executed not by a viral enzyme but by the hijacked host endosomal sorting complexes required for transport (ESCRT) machinery.

This review synthesizes current knowledge on how HIV-1 Gag polyprotein recruits and coordinates the ESCRT pathway. We detail the critical roles of the PTAP and YPX_nL late-domain motifs in engaging Tsg101 (ESCRT-I) and ALIX adaptors, which nucleate the assembly of constrictive ESCRT-III polymers and the VPS4 ATPase to catalyze membrane fission. We examine the plasticity of these recruitment pathways, the regulatory influence of ubiquitination, and how cell-type-specific factors impact budding efficiency. Furthermore, we assess emerging connections between ESCRT function, viral pathogenesis, and therapeutic opportunities.

The ESCRT-dependent budding of HIV-1 is a robust yet vulnerable process, characterized by redundant entry points converging on an essential core scission engine. This mechanistic understanding reveals critical virus-host interfaces that present promising targets for novel antiviral strategies aimed at disrupting this late stage of the viral life cycle.