Insights into the function of ESCRT and its role in enveloped virus infection

Abstract

The endosomal sorting complex required for transport (ESCRT) is an essential molecular machinery in eukaryotic cells that facilitates the invagination of endosomal membranes, leading to the formation of multivesicular bodies (MVBs). It participates in various cellular processes, including lipid bilayer remodeling, cytoplasmic separation, autophagy, membrane fission and re-modeling, plasma membrane repair, as well as the invasion, budding, and release of certain enveloped viruses. The ESCRT complex consists of five complexes, ESCRT-0 to ESCRT-III and VPS4, along with several accessory proteins. ESCRT-0 to ESCRT-II form soluble complexes that shuttle between the cytoplasm and membranes, mainly responsible for recruiting and transporting membrane proteins and viral particles, as well as recruiting ESCRT-III for membrane neck scission. ESCRT-III, a soluble monomer, directly participates in vesicle scission and release, while VPS4 hydrolyzes ATP to provide energy for ESCRT-III complex disassembly, enabling recycling. Studies have confirmed the hijacking of ESCRT complexes by enveloped viruses to facilitate their entry, replication, and budding. Recent research has focused on the interaction between various components of the ESCRT complex and different viruses. In this review, we discuss how different viruses hijack specific ESCRT regulatory proteins to impact the viral life cycle, aiming to explore commonalities in the interaction between viruses and the ESCRT system.

SARS-CoV-2 3CLpro Main Protease Drives Cytoskeletal Reorganization and Tunnelling Nanotube Formation for Stealth Intercellular Infection

“…Knockdown of signal transducing adapter molecule 1 (STAM) results in increased length of cell projections 67 , suggesting that STAM is inhibitory. STAM is a component of the endosomal sorting complexes required for transport (ESCRT)-0 complex that mediates membrane remodelling, vesicular transport and autophagy, and is hijacked by enveloped viruses to mediate budding 68 . STAM was cleaved by 3CL pro (Extended Data Fig.…”

Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design

“…As previously discussed, specific viral proteins exploit the exosome biogenesis pathway to facilitate virus budding. It has been shown that transmembrane subunits of viral envelope proteins, including those of HIV, can interact with components of the ESCRT machinery, such as TSG101 [ 264 ]. These properties, which are found in the proteins of various viruses (e.g., the VSV-G protein or the Nef protein of HIV), have been exploited to direct proteins of interest to exosomes [ 265 ].…”

Research progress on the mechanism of exosome-mediated virus infection

“…HSV-1 is a nervous system pathogen, which uses its own virus-encoded protein and host ESCRT mechanism to promote viral budding ( Button et al., 2020 ). Unlike other enveloped viruses, HSV-1 does not require TSG101 or ALIX, a protein containing the Bro1 domain, to recruit or activate ESCRT-1 ( Wang C. et al., 2023 ). HSV-1 capsid uses nucleoplasmic ESCRT to obtain a lipid envelope from the inner nuclear membrane (INM) and then fuses with the outer nuclear membranes (ONM) ( Wilhelmsen et al., 2005 ).…”