Extracellular vesicles (EVs) are involved in numerous processes during infections by both enveloped and non-enveloped viruses. Among them, herpes simplex virus type-1 (HSV-1) modulates secretory pathways, allowing EVs to exit infected cells. Many characteristics regarding the mechanisms of viral spread are still unidentified, and as such, secreted vesicles are promising candidates due to their role in intercellular communications during viral infection. Another relevant role for EVs is to protect virions from the action of neutralizing antibodies, thus increasing their stability within the host during hematogenous spread. Recent studies have suggested the participation of EVs in HSV-1 spread, wherein virion-containing microvesicles (MVs) released by infected cells were endocytosed by naïve cells, leading to a productive infection. This suggests that HSV-1 might use MVs to expand its tropism and evade the host immune response. Researchers from the Universidad Autónoma de Madrid briefly describe the current knowledge about the involvement of EVs in viral infections in general, with a specific focus on recent research into their role in HSV-1 spread. Implications of the autophagic pathway in the biogenesis and secretion of EVs are also discussed.
Models of biogenesis and secretion of MV-enclosed HSV-1 virions
(A) The canonical egress of HSV-1 entails the fusion of a two-membraned viral particle with the plasma membrane, giving rise to an extracellular free enveloped virion. In this model, the viral envelope is derived from the TGN/endosomes. (B) Alternatively, this structure might exit the cell after shedding of the plasma membrane, resulting in a three-membraned viral particle, which would correspond to an enveloped virion enclosed within a shedding MV. (C) According to this model, vesicles/tubules originating from the autophagic pathway wrap around the nucleocapsid, giving rise to a viral particle surrounded by a double membrane. Then, this structure would reach the plasma membrane and, after fusion, a viral particle surrounded by a single membrane would exit the cell. (D) In an alternative model, the two-membraned viral particle might exit the cell not by fusion, but by shedding of the plasma membrane, giving rise to a three-membraned viral particle.