Abstract

Extracellular vesicles have recently emerged as a novel mode of viral transmission exploited by naked viruses to exit host cells through a nonlytic pathway. Extracellular vesicles can allow multiple viral particles to collectively traffic in and out of cells, thus enhancing the viral fitness and diversifying the transmission routes while evading the immune system. This has been shown for several RNA viruses that belong to the Picornaviridae, Hepeviridae, Reoviridae, and Caliciviridae families; however, recent studies also demonstrated that the BK and JC viruses, two DNA viruses that belong to the Polyomaviridae family, use a similar strategy. In this review, we provide an update on recent advances in understanding the mechanisms used by naked viruses to hijack extracellular vesicles, and we discuss the implications for the biology of polyomaviruses.

Highlights

  • Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are physiologically released from cells and carry proteins, nucleic acids, lipids, or metabolites to recipient cells [1]

  • They are produced via different mechanisms (Figure 1): (i) direct budding from the plasma membrane to form microvesicles, called ectosomes; (ii) budding of intraluminal vesicles (ILVs) during the process of multivesicular body (MVB) formation and release of exosomes in the extracellular environment as a result of the fusion of MVBs with the plasma membrane; (iii) autophagosome-mediated exit without lysis or secretory autophagy that releases single-membrane vesicles after the fusion of double-membraned autophagosomes with the plasma membrane; (iv) apoptosis that generates apoptotic bodies

  • For 50 years, these viruses were considered as naked particles released by cell lysis, but we and the Atwood Laboratory recently described that they hijack EVs to be released through a nonlytic pathway and to be transmitted en bloc to target cells

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Summary

Introduction

Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are physiologically released from cells and carry proteins, nucleic acids, lipids, or metabolites to recipient cells [1] They are produced via different mechanisms (Figure 1): (i) direct budding from the plasma membrane to form microvesicles, called ectosomes; (ii) budding of intraluminal vesicles (ILVs) during the process of multivesicular body (MVB) formation and release of exosomes in the extracellular environment as a result of the fusion of MVBs with the plasma membrane; (iii) autophagosome-mediated exit without lysis or secretory autophagy that releases single-membrane vesicles after the fusion of double-membraned autophagosomes with the plasma membrane; (iv) apoptosis that generates apoptotic bodies. In the last decade, several studies evidenced that various naked RNA viruses hijack EVs to exit host cells through a nonlytic pathway.

Release of EV-Associated Virions
Entry of EV-Associated Virions
Neutralization of EV-Associated Virions
Consequences for the Physiopathology of Polyomaviruses
Concluding Remarks and Future Directions
Findings
Model of the andand
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