Abstract
Extracellular vesicles (EVs) constitute a heterogeneous group of vesicles released by all types of cells that play a major role in intercellular communication. The field of EVs started gaining attention since it was realized that these vesicles are not waste bags, but they carry specific cargo and they communicate specific messages to recipient cells. EVs can deliver different types of RNAs, proteins, and lipids from donor to recipient cells and they can influence recipient cell functions, despite their limited capacity for cargo. EVs have been compared to viruses because of their size, cell entry pathways, and biogenesis and to viral vectors because they can be loaded with desired cargo, modified, and re-targeted. These properties along with the fact that EVs are stable in body fluids, they can be produced and purified in large quantities, they can cross the blood–brain barrier, and autologous EVs do not appear to cause major adverse effects, have rendered them attractive for therapeutic use. Here, we discuss the potential for therapeutic use of EVs derived from virus infected cells or EVs carrying viral factors. We have focused on six major concepts: (i) the role of EVs in virus-based oncolytic therapy or virus-based gene delivery approaches; (ii) the potential use of EVs for developing viral vaccines or optimizing already existing vaccines; (iii) the role of EVs in delivering RNAs and proteins in the context of viral infections and modulating the microenvironment of infection; (iv) how to take advantage of viral features to design effective means of EV targeting, uptake, and cargo packaging; (v) the potential of EVs in antiviral drug delivery; and (vi) identification of novel antiviral targets based on EV biogenesis factors hijacked by viruses for assembly and egress. It has been less than a decade since more attention was given to EV research and some interesting concepts have already been developed. In the coming years, additional information on EV biogenesis, how they are hijacked and utilized by pathogens, and their impact on the microenvironment of infection is expected to indicate avenues to optimize existing therapeutic tools and develop novel approaches.
Highlights
Extracellular vesicles (EVs) are released by all cell types, including bacteria, archaea, fungi, and eukaryotes (Deatheragea and Cooksona, 2012)
Nagashima et al (2017) worked with the Hepatitis E Virus (HEV), another non-enveloped virus, and in parallel with Emerson et al (2010) they demonstrated that release of HEV from cultured cells depends on the ORF3 protein and requires an intact PXXP motif in the ORF3 protein
Structures resembling MVBs were found containing virions and small vesicles, which were fused with the plasma membrane (PM) and released both virions and vesicles in the extracellular space. These results suggest that human herpes virus-6 (HHV-6) hijacks the EV biogenesis machinery to mediate its envelopment and release
Summary
Extracellular vesicles (EVs) are released by all cell types, including bacteria, archaea, fungi, and eukaryotes (Deatheragea and Cooksona, 2012). With the identification of biological roles for EVs, one emerging area is how the production and content of EVs may be modulated during infections and how these EVs could contribute to viral-mediated pathogenesis (Madison and Okeoma, 2015; Kalamvoki and Deschamps, 2016) It appears that there is an overlap between EV biogenesis and virion assembly or egress from the host cells (Gould et al, 2003; Wurdinger et al, 2012; Schorey et al, 2015; van Dongen et al, 2016; Sadeghipour and Mathias, 2017; Dogrammatzis et al, 2019). The best example to illustrate how the ESCRT pathway is utilized during virus budding is the process of HIV-1 assembly (Lorizate et al, 2013)
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