Extracellular vesicles are the Trojan horses of viral infection

Abstract

Extracellular vesicles have recently emerged as a novel mode of viral propagation exploited by both enveloped and non-enveloped viruses. In particular non-enveloped viruses utilize the hosts' production of extracellular vesicles to exit from cells non-lytically and to hide and manipulate the immune system. Moreover, challenging the long held idea that viruses behave as independent genetic units, extracellular vesicles enable multiple viral particles and genomes to collectively traffic in and out of cells, which can promote genetic cooperativity among viral quasispecies and enhance the fitness of the overall viral population.

Figure 1

Diagram of extracellular vesicles mediating the non-lytic transmission of populations of virions and viral nucleic acids between two cells. RNA virus replication results in viral progeny that is a mixture of quasispecies. Extracellular vesicles with phosphatidylserine-enriched membranes, derived from multivesicular bodies (MVB) or from autophagosomes, capture populations of quasispecies from the cytoplasm, either in assembled viral particle form (e.g. poliovirus, HAV) or as naked viral RNA (e.g. HCV) (cell 1). These populations of quasispecies in vesicles are delivered to a new host cell (cell 2), giving rise to a high multiplicity of infection. This in turn enhances the replicative fitness of these quasispecies by promoting cooperative interactions among them including recombination among genomes, sharing viral machinery for translation, RNA synthesis, assembly as well as restricting the innate immune defenses of the host cell.