The regulation of Endosomal Sorting Complex Required for Transport and accessory proteins in multivesicular body sorting and enveloped viral budding - An overview

Abstract

ESCRT (Endosomal sorting complex required for transport) machinery drives different cellular processes such as endosomal sorting, organelle biogenesis, vesicular trafficking, maintenance of plasma membrane integrity, membrane fission during cytokinesis and enveloped virus budding. The normal cycle of assembly and disassembly of some ESCRT complexes at the membrane requires the AAA-ATPase vacuolar protein sorting 4 (Vps4p). A number of ESCRT proteins are hijacked by clinically significant enveloped viruses including Ebola, and Human Immunodeficiency Virus (HIV) to enable enveloped virus budding and Vps4p provides energy for the disassembly/recycling of these ESCRT proteins. Several years ago, the failure of the terminal budding process of HIV following Vps4 protein inhibition was published; although at that time a detailed understanding of the molecular players was missing. However, later it was acknowledged that the ESCRT machinery has a role in enveloped virus budding from cells due to its role in the multivesicular body (MVB) sorting pathway. The MVB sorting pathway facilitates several cellular activities in uninfected cells, such as the down-regulation of signaling through cell surface receptors as well as the process of viral budding from infected host cells. In this review, we focus on summarising the functional organisation of ESCRT proteins at the membrane and the role of ESCRT machinery and Vps4p during MVB sorting and enveloped viral budding.

Single-Cell RNA-seq Identifies Cell Subsets in Human Placenta That Highly Expresses Factors Driving Pathogenesis of SARS-CoV-2

“…We profiled the mRNA levels of 27 host proteins involved in human ESCRT for viruses (Ahmed et al, 2019) and mRNA levels of 30 proteins involved in viral replication (de Wilde et al, 2018) in placental cells that co-express ACE2 and TMPRSS2 in first and second trimester (Supplementary Table 1). We also analyzed the transcript profiles of 332 human proteins that physically interact with SARS-CoV-2 in placental cells that co-express ACE2 and TMPRSS2 (Gordon et al, 2020).…”

“…This course requires a network of host factors to create an optimal environment for facilitating viral entry, gene expression, RNA synthesis and virus release (de Wilde et al, 2018). Further, most enveloped viruses bud at the plasma membrane by recruiting the host endosomal sorting complex required for transport (ESCRT) machinery (Ahmed et al, 2019;Gatta and Carlton, 2019). While the precise host proteins in SARS-CoV-2 entry and replication are not yet understood, its host interactome has been characterized (Gordon et al, 2020).…”

The Dichotomous Role of Extracellular Vesicles in the Central Nervous System

“…

Similarities between EV Release and Viral Budding Emerging evidence suggests that the molecular machinery required for EV release and enveloped virus budding share many important characteristics. Viruses including herpes simplex virus 1, Ebola virus, rabies virus, and human immunodeficiency virus (HIV) have evolved the capacity to hijack host cell ESCRT machinery, which plays a key role in EV biogenesis to promote budding ( Ahmed et al., 2019 ; Votteler and Sundquist, 2013 ). One particular protein that is important for the ESCRT pathway linking viral budding and EV release is Alix (also known as Pdcd6ip).

…”

Protein Amphipathic Helix Insertion: A Mechanism to Induce Membrane Fission

“…Class III: Active mechanism, reverse topology. Examples: fission mediated by the ESCRT machinery (Chiaruttini and Roux, 2017;Schöneberg et al, 2017;Stoten and Carlton, 2018;Ahmed et al, 2019;Gatta and Carlton, 2019), bacterial cell division (Bohuszewicz et al, 2016;Vedyaykin et al, 2019) and archaeal cell division (Caspi and Dekker, 2018). Of note, Vps4 ATPase (Monroe et al, 2014;Caspi and Dekker, 2018), BDLP1 containing N-terminal GTPase domain (Bohuszewicz et al, 2016), and CdvC containing ATPase subunit (Caspi and Dekker, 2018) proteins provide energy for the ESCRT pathway, bacterial cell division, and archaeal cell division, respectively.…”