Abstract

The main protein components of the multivesicular body (MVB) pathway include endosomal sorting complexes required for transport (ESCRT) and vacuolar protein sorting 4 (VPS4). Recent studies revealed that late domain motifs of enveloped viruses, such as PTAP, YPxL and PPxY (x indicates any amino acid residues), can bind separately to tumor susceptibility gene 101 (TSG101), ALG-2-interacting protein X (ALIX) and neuronal precursor cell-expressed developmentally downregulated 4 (NEDD4), to directly or indirectly recruit ESCRT and VPS4 for budding and egress. Also discovered recently, MVB proteins can be regulated by the host cell to block virus budding, for example by conjugation of interferon-stimulated gene 15 (ISG15) protein to ESCRT III and NEDD4, phosphorylation of VPS37C by TANK-binding kinase 1 (TBK1) and phosphorylation of MVB12. Thus, the MVB pathway is emerging as a newly discovered battlefield for the gameplay between virus and host, opening an avenue to design novel antiviral therapeutics.

Key words: Multivesicular body, virus budding, late domain motif, ISGylation, TANK-binding kinase 1