Abstract
Exosomes are small nanovesicles of about 100 nm in diameter that act as intercellular messengers because they can shuttle RNA, proteins and lipids between different cells. Many studies have found that exosomes also play various roles in viral pathogenesis. Hepatitis A virus (HAV; a picornavirus) and Hepatitis C virus (HCV; a flavivirus) two single strand plus-sense RNA viruses, in particular, have been found to use exosomes for viral transmission thus evading antibody-mediated immune responses. Paradoxically, both viral exosomes can also be detected by plasmacytoid dendritic cells (pDCs) leading to innate immune activation and type I interferon production. This article will review recent findings regarding these two viruses and outline how exosomes are involved in their transmission and immune sensing.
Highlights
Exosomes, believed to be nothing more than expelled cellular waste containers after their discovery in the early 1980s [1,2,3], have since been found to act as important intercellular messengers carrying functional RNAs, proteins and lipids that can induce phenotypic changes in recipient cells [4]
Many proteins have been found to be involved in exosome/multivesicular bodies (MVBs) biogenesis and chief among those are the endosomal sorting complexes required for transport (ESCRTs) ESCRT independent mechanisms for MVB formation have been described [7,8,9]
What is needed for Hepatitis C virus (HCV) exosome release, are the ESCRT proteins chromatin-modifying protein 4B (CHMP4B) and tumour susceptibility gene 101 (TSG101) as well as the membrane trafficking regulator Annexin A2 (ANXA2), which are all part of the canonical machinery involved in MVB biogenesis and exosome secretion [20]
Summary
Exosomes, believed to be nothing more than expelled cellular waste containers after their discovery in the early 1980s [1,2,3], have since been found to act as important intercellular messengers carrying functional RNAs, proteins and lipids that can induce phenotypic changes in recipient cells [4]. Many proteins have been found to be involved in exosome/MVB biogenesis and chief among those are the endosomal sorting complexes required for transport (ESCRTs) ESCRT independent mechanisms for MVB formation have been described [7,8,9]. It is not clear whether different subpopulations of exosomes are created via different mechanisms of MVB biogenesis or whether incorporation of specific exosomal proteins leads to distinct classes of exosome-like vesicles. Exosomes are secreted by almost all cell types and can be found in all bodily fluids but the exact mechanisms of exosomal targeting to specific cell types (if this occurs in vivo) and cargo release remain to be elucidated [11,12,13]
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