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Insane in the Membrane: Glial Extracellular Vesicles Transmit Polyomaviruses
Marianita Santiana1, Nihal Altan-Bonnet2
1Laboratory of Host-Pathogen Dynamics, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Mbio
|May 30, 2019
Summary
JC polyomavirus (JCPyV), a DNA virus, uses extracellular vesicles (EVs) for transmission between cells. This EV-mediated spread is highly infectious and bypasses antibody defenses, potentially explaining JCPyV
Area of Science:
- Virology
- Cell Biology
- Neuroscience
Background:
- Extracellular vesicles (EVs) are recognized vehicles for intercellular communication and pathogen transport.
- RNA viruses are predominantly transmitted via EVs, but DNA virus transmission through EVs is less understood.
- JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a severe neurological disease.
Purpose of the Study:
- To investigate the role of extracellular vesicles (EVs) in the transmission of the double-stranded DNA (dsDNA) virus, JC polyomavirus (JCPyV).
- To determine if JCPyV can be released from and transmitted to glial cells via EVs.
- To assess the infectiousness and characteristics of EV-mediated JCPyV transmission.
Main Methods:
- Utilized cell culture models to study JCPyV release and uptake.
- Employed techniques to isolate and characterize EVs containing JCPyV.
- Assessed the infectivity of JCPyV transmitted through EVs.
Main Results:
- Demonstrated that JC polyomavirus (JCPyV), a dsDNA virus, is released from and transmitted to glial cells via extracellular vesicles (EVs).
- EV-mediated JCPyV transmission is highly infectious and independent of known viral receptors (LSTc and 5-HT2).
- JCPyV within EVs is protected from neutralizing antibodies.
Conclusions:
- Extracellular vesicles (EVs) represent a novel and significant route for JC polyomavirus (JCPyV) transmission.
- EV-mediated spread may explain JCPyV's dissemination into the central nervous system (CNS) and its virulence.
- This discovery opens new avenues for understanding and potentially targeting JCPyV pathogenesis.
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