Virus budding and the ESCRT pathway - PubMed (original) (raw)

Review

Virus budding and the ESCRT pathway

Jörg Votteler et al. Cell Host Microbe. 2013.

Abstract

Enveloped viruses escape infected cells by budding through limiting membranes. In the decade since the discovery that HIV recruits cellular ESCRT (endosomal sorting complexes required for transport) machinery to facilitate viral budding, this pathway has emerged as the major escape route for enveloped viruses. In cells, the ESCRT pathway catalyzes analogous membrane fission events required for the abscission stage of cytokinesis and for a series of "reverse topology" vesiculation events. Studies of enveloped virus budding are therefore providing insights into the complex cellular mechanisms of cell division and membrane protein trafficking (and vice versa). Here, we review how viruses mimic cellular recruiting signals to usurp the ESCRT pathway, discuss mechanistic models for ESCRT pathway functions, and highlight important research frontiers.

Copyright © 2013 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Figures

Figure 1

Figure 1. ESCRT pathway recruitment

Cellular and viral adaptor proteins and complexes that recruit early-acting ESCRT factors and NEDD4 family ubiquitin E3 ligases to different sites of ESCRT-dependent membrane fission are depicted schematically. The figure emphasizes how different retroviruses hijack the ESCRT pathway using late assembly domains within their Gag polyproteins (yellow background, Gag proteins in orange, with their constituent domains shown schematically), and how these interactions mimic analogous interactions between cellular adaptors (underlined) and ESCRT factors (white background). Polyubiquitin chains are depicted as connected yellow hexagons, solid arrows denote known protein-protein interactions, dashed arrows denote inferred or indirect protein-protein interactions, and question marks indicate that the site(s) of ubiquitin attachment are uncertain (see text). Abbreviations: HIV, Human Immunodeficiency Virus; RSV, Rous sarcoma virus; EIAV, Equine Infectious Anemia Virus; MVB, multivesicular body; ART, arrestin-related trafficking adaptor. For illustration purposes, we selected retroviruses that bud primarily through P(T/S)AP (HIV-1), PPXY (RSV) and YPXL (EIAV) late assembly domains, but note that these viruses all also use auxiliary late assembly domains, including an YPXL motif in RSV (not shown) (Dilley et al., 2010).

Figure 2

Figure 2. Multiple late assembly domains of HIV-1 Gag recruit different ESCRT-associated factors that may work together to facilitate virus budding

The model suggests how three different early-acting ESCRT-associated factors recruited by HIV-1 Gag -- NEDD4L (pink), ESCRT-I (red) and dimeric ALIX (dark blue) -- could work together in a stepwise fashion to facilitate virus budding. The three regions of HIV-1 Gag are depicted in yellow (MA), orange (CA) and red (NC, bound to blue RNA), the subunits of the trimeric viral Env protein are depicted in blue (SU/gp120) and pink (TM/gp41), and ESCRT-III proteins (light green) are depicted schematically as either polymeric filaments (central panel, light green ring) or soluble, autoinhibited subunits (right panel, discrete subunits). ESCRT-I is missing from the final panel because the ultimate fate of this complex is not yet clear.

Similar articles

Cited by

References

    1. Agromayor M, Martin-Serrano J. Knowing when to cut and run: mechanisms that control cytokinetic abscission. Trends Cell Biol. 2013 Epublication ahead of print. - PubMed
    1. Akers JC, Gonda D, Kim R, Carter BS, Chen CC. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. Journal of neuro-oncology 2013 - PMC - PubMed
    1. Babst M, Katzmann D, Estepa-Sabal E, Meerloo T, Emr S. Escrt-III. An endosome-associated heterooligomeric protein complex required for mvb sorting. Dev Cell. 2002;3:271–282. - PubMed
    1. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14:677–685. - PubMed
    1. Baumgartel V, Ivanchenko S, Dupont A, Sergeev M, Wiseman PW, Krausslich HG, Brauchle C, Muller B, Lamb DC. Live-cell visualization of dynamics of HIV budding site interactions with an ESCRT component. Nat Cell Biol. 2011;13:469–474. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources