Abstract

Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules. The exchange of EVs between cells facilitates intercellular communication, amplification of cellular responses, immune response modulation, and perhaps alterations in viral pathogenicity. EVs serve a dual role in inhibiting or enhancing viral infection and pathogenesis. This review examines the current literature on EVs to explore the complex role of EVs in the enhancement, inhibition, and potential use as a nanotherapeutic against clinically relevant viruses, focusing on neurotropic viruses: Zika virus (ZIKV) and human immunodeficiency virus (HIV). Overall, this review’s scope will elaborate on EV-based mechanisms, which impact viral pathogenicity, facilitate viral spread, and modulate antiviral immune responses.

Highlights

  • Most cells can release extracellular vesicles (EVs), membrane vesicles containing various proteins, nucleic acids, enzymes, and signaling molecules

  • Exosomes may be separated from EVs using ultrafiltration to isolate exosomes within a sample. They pass through filters with increasingly small pore size, which traps particles of higher molecular mass and allows EV exosomes and other nanoparticles to flow through Bhattacharjee C et al [21] 2002

  • EV biogenesis facilitates viral spread when the following conditions are met: (1) Viral proteins or RNA must reach the intraluminal vesicles (ILVs); components of Dengue virus (DENV), vesicular stomatitis virus (VSV), and hepatitis C virus (HCV) have all been identified in ILVs [6]. (2) Exosomes must interact with target cells releasing their infectious cargo into the extracellular space; recipient cells receive both viral and exosome constituents upon exosome entry into the cytoplasm

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Summary

Isolation of EVs

Various methods used for EV isolation include differential ultracentrifugation, immunomagnetic-bead. The most based separation, ultrafiltration, nanoplasmon-enhanced scattering (nPES), and on-chip exosome commonly used method and the gold standard in EV isolation is differential ultracentrifugation Livshits isolation Yu LL et al [11] 2018. Given the overlap in the size of exosomes and microvesicles size, labor-intensive and time-consuming with a low yield. Despite these disadvantages, DC is considered the EV pellet likely consists of both vesicle types. Can be labor-intensive and time-consuming with a low yield Despite these disadvantages, DC is considered the gold standard for exosome isolation. After the sample has been incubated with the antibody-labeled magnetic beads, the exosomecomplexes formed are added to the separation column and retained in the column upon applying the magnetic field This method may compromise the captured exosome integrity but assures highly purified exosomes, unlike the DC method. The primary disadvantage of immunoaffinity is the inability to separate the beads from the exosomes, preventing or limiting downstream applications

Density Gradient—OptiPrepTM
Chromatography
Precipitation
Ultrafiltration
Lab-On-Chip Exosome Isolation
Exosomal Content and Characterization
Role of EVs in the Pathogenesis of Viral Infections
Picornaviridae and Togaviridae
Herpesviridae
Filoviridae
Paramyxoviridae
Orthomyxoviridae
Hepadnaviridae
Flaviviridae
EV-Mediated Restriction of ZIKV Pathogenesis
EV-Mediated Enhancement of ZIKV Neuropathology
Retroviridae
EV Interaction with Host Cell Restriction Factors and HIV
Immune Cell-Derived EVs and Antiviral Effects
EV-Mediated Enhancement of HIV-1 Infection
Coronaviridae
4.10. Polyomaviridae
Therapeutic Potential of EVs as Antiviral Agents
Findings
Conclusions
Full Text
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