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

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Abstract

The endosomal sorting complex required for transport (ESCRT) system consists of peripheral membrane protein complexes ESCRT-0, -I, -II, -III VPS4-VTA1, and ALIX homodimer. This system plays an important role in the degradation of non-essential or dangerous plasma membrane proteins, the biogenesis of lysosomes and yeast vacuoles, the budding of most enveloped viruses, and promoting membrane shedding of cytokinesis. Recent results show that exosomes and the ESCRT pathway play important roles in virus infection. This review mainly focuses on the roles of exosomes and the ESCRT pathway in virus assembly, budding, and infection of enveloped viruses. The elaboration of the mechanism of exosomes and the ESCRT pathway in some enveloped viruses provides important implications for the further study of the infection mechanism of other enveloped viruses.

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Clotilde Théry, Kenneth W Witwer, Elena Aikawa … (2019)

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes.

Joanna Kowal, Guillaume Arras, Marina Colombo … (2016)

Extracellular vesicles (EVs) have become the focus of rising interest because of their numerous functions in physiology and pathology. Cells release heterogeneous vesicles of different sizes and intracellular origins, including small EVs formed inside endosomal compartments (i.e., exosomes) and EVs of various sizes budding from the plasma membrane. Specific markers for the analysis and isolation of different EV populations are missing, imposing important limitations to understanding EV functions. Here, EVs from human dendritic cells were first separated by their sedimentation speed, and then either by their behavior upon upward floatation into iodixanol gradients or by immuno-isolation. Extensive quantitative proteomic analysis allowing comparison of the isolated populations showed that several classically used exosome markers, like major histocompatibility complex, flotillin, and heat-shock 70-kDa proteins, are similarly present in all EVs. We identified proteins specifically enriched in small EVs, and define a set of five protein categories displaying different relative abundance in distinct EV populations. We demonstrate the presence of exosomal and nonexosomal subpopulations within small EVs, and propose their differential separation by immuno-isolation using either CD63, CD81, or CD9. Our work thus provides guidelines to define subtypes of EVs for future functional studies.

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Biogenesis and secretion of exosomes.

Joanna Kowal, Mercedes Tkach, Clotilde Théry (2014)

Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist. Copyright © 2014 Elsevier Ltd. All rights reserved.