As part of the HCMV Vesicle Formation Complex, Vps4 controls the release of ESCRT complexes from membranes. Upstream ESCRT complexes ESCRT-I and ESCRT-II are believed to work in parallel to recruit the cargo, whereas Vps4 and ESCRT-III work in series. Virus envelopment occurs by budding into endosomal vesicles, which fuse with the plasma membrane to release virions to the extracellular space. Accumulation of viral glycoproteins gM-gN and ESCRT proteins at the periphery of AC support this model of viral egress, where these proteins provide essential functions such as envelopment and endosomal budding before viral exit.
Both Vps4A and CHMP1A are localized in the vicinity of viral cytoplasmic assembly compartments, sites of viral maturation that develop in CMV-infected cells. Localization of CHMP1A and Vps4A proteins in the vicinity of AC, where the final steps in virus maturation and envelopment occur, indicates an important role of ESCRT pathway during these processes in HCMV life cycle. Both Vps4A and CHMP1A, the ESCRT-III component, influence the outcome of ESCRT recruitment via upstream parallel pathways using Tsg101, ALIX, or HECT-Ub ligases. Vps4A contributes to all three known primary mechanisms of ESCRT recruitment by viruses. Tsg101, a component of ESCRT-I, normally functions to deliver ubiquitinated transmembrane proteins to MVBs. ALIX binds to Tsg101 in addition to ESCRT-III protein CHMP-4B, thus linking ESCRT-I and ESCRT-III.