The Interplay between ESCRT and Viral Factors in the Enveloped Virus Life Cycle

Abstract

Viruses are obligate parasites that rely on host cellular factors to replicate and spread. The endosomal sorting complexes required for transport (ESCRT) system, which is classically associated with sorting and downgrading surface proteins, is one of the host machineries hijacked by viruses across diverse families. Knowledge gained from research into ESCRT and viruses has, in turn, greatly advanced our understanding of many other cellular functions in which the ESCRT pathway is involved, e.g., cytokinesis. This review highlights the interplay between the ESCRT pathway and the viral factors of enveloped viruses with a special emphasis on retroviruses.

Keywords: ESCRT; NEDD4; budding; enveloped virus; late domain; retrovirus.

Figure 1

Schematic diagrams of the mammalian core ESCRT protein complexes. Direct contacts are made to show the interaction among the ESCRT components e.g., VPS28 and EAP45, and EAP20 and CHMP6. Double-headed arrows denote the intermolecular interactions between ALIX and TSG101 and ALIX and CHMP4B.

Figure 2

Multifaceted roles of ESCRT in the enveloped virus life cycles. The extracellular virus budding at the plasma membrane (PM) is exemplified with a late assembly and budding event of HIV. HIV, and other enveloped viruses, e.g., filovirus, rhabdovirus, and arenavirus (not shown), also utilises ubiquitination in gaining access to the ESCRT system for virus export. HSV-1 is unique as two steps of envelopments occur with the requirement of ALIX (ALG2-interacting protein X) and ESCRT-III for the nuclear or primary envelopment while a unique viral encoded ESCRT-III-like protein pUL51 is thought to be involved in membrane constriction for the secondary envelopment. ESCRT-II is involved in ribonucleoprotein trafficking for both HIV and HBV. The color scheme is the same as those in Figure 1 unless stated otherwise. Question marks denote the possibility of the involvement of ESCRT or other factors at various stages of virus life cycles. AMOT: angiomotin. ER: endoplasmic reticulum. EE: early endosome. MVB: multivesicular body.