Why Cells and Viruses Cannot Survive without an ESCRT

Abstract

Intracellular organelles enwrapped in membranes along with a complex network of vesicles trafficking in, out and inside the cellular environment are one of the main features of eukaryotic cells. Given their central role in cell life, compartmentalization and mechanisms allowing their maintenance despite continuous crosstalk among different organelles have been deeply investigated over the past years. Here, we review the multiple functions exerted by the endosomal sorting complex required for transport (ESCRT) machinery in driving membrane remodeling and fission, as well as in repairing physiological and pathological membrane damages. In this way, ESCRT machinery enables different fundamental cellular processes, such as cell cytokinesis, biogenesis of organelles and vesicles, maintenance of nuclear–cytoplasmic compartmentalization, endolysosomal activity. Furthermore, we discuss some examples of how viruses, as obligate intracellular parasites, have evolved to hijack the ESCRT machinery or part of it to execute/optimize their replication cycle/infection. A special emphasis is given to the herpes simplex virus type 1 (HSV-1) interaction with the ESCRT proteins, considering the peculiarities of this interplay and the need for HSV-1 to cross both the nuclear-cytoplasmic and the cytoplasmic-extracellular environment compartmentalization to egress from infected cells.

EhVps23: A Component of ESCRT-I That Participates in Vesicular Trafficking and Phagocytosis of Entamoeba histolytica

“…The endosomal sorting complex required for transport (ESCRT), formed by the ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III complexes, and accessory proteins, is one of the main players in vesicle trafficking. Proteins that conform these complexes differ in sequence along organisms through the evolutionary scale (Leung et al, 2008), but conserve their functional domains that allow them to participate in cell division, endocytosis, virus budding and other functions (Calistri et al, 2021). In E. histolytica, ESCRT machinery is involved in phagocytosis (Lopez-Reyes et al, 2010;Avalos-Padilla et al, 2015;Avalos-Padilla et al, 2018), a virulence landmark of the parasite (Garcıá-Rivera et al, 1999).…”

The Role of Exosome and the ESCRT Pathway on Enveloped Virus Infection

“…After assembly of progeny virions, they first bud from the nuclear membrane to cytoplasm and obtain a lipid envelope. They then enter the plasma membrane through a second budding and obtain the second envelope before being released into the extracellular environment [128]. HSV-1 exploit nucleoplasmic ESCRTs to promote inner nuclear membrane (INM) remodeling and fission in the first envelopment step [128].…”

“…They then enter the plasma membrane through a second budding and obtain the second envelope before being released into the extracellular environment [128]. HSV-1 exploit nucleoplasmic ESCRTs to promote inner nuclear membrane (INM) remodeling and fission in the first envelopment step [128]. ESCRT-III is recruited to the INM during the budding of HSV-1 from the nucleus, mediating the budding of HSV-1 from the INM and regulating the integrity of the INM [129].…”

Novel Tsg101 Binding Partners Regulate Viral L Domain Trafficking

“…UEV proteins play key roles with E3 ligases in control of protein trafficking, stability and DNA replication, vital functions that viruses can harness for their own production. The discovery that Tsg101 interacts with the HIV-1 structural precursor polyprotein, Gag, linked the ESCRT machinery in human cells to viral egress and much is now known about the process ( [1][2][3], reviewed in [4][5][6][7]). Interestingly, viruses may exploit the ESCRT machinery at different replication stages, e.g., the retrovirus HIV-1 utilizes ESCRT factors at late stages of particle assembly to bud from the plasma membrane; herpes viruses, including herpes simplex viruses (HSV) and Epstein-Barr virus (EBV), bud initially from the inner nuclear membrane and later undergoing a second envelopment in the cytoplasm before finally exiting through the secretory pathway.…”

“…The UEV domain mediates these Tsg101 functions through the P(T/S)AP-and Ub-binding functions. The region downstream of the UEV domain in Tsg101 interacts with other proteins, including the binding partners with which it forms ESCRT-I, a complex that functions with ESCRT-0, -II, -III, and the ATPase Vps4 in endocytic trafficking (reviewed in [4,6,14,15]). As the member on which the partners nucleate, Tsg101 thus controls ESCRT-I formation and plays an essential scaffolding and mechanical role in addition to functioning as a conduit to ESCRT-III [8].…”