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Published on: July 13, 2019
Archetype JC polyomavirus DNA associated with extracellular vesicles circulates in human plasma samples
Stefano Scribano1, Mirko Guerrini1, Rosaria Arvia1
1Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Background:
JC polyomavirus (JCPyV) establishes a stable and successful interaction with the host, causing progressive multifocal leukoencephalopathy (PML) in immunocompromised subjects. Recently, it has been reported that JCPyV, like other viruses, may exploit extracellular vesicles (EV) in cell cultures.
Objective:
To investigate the presence of JCPyV-DNA in EV circulating in human plasma obtained from patients at risk for PML.
Study Design:
JCPyV-DNA status was studied in EV obtained from 170 plasma samples collected from 120 HIV positive patients and 50 healthy donors. EV were extracted from plasma and characterized by Nanoparticle tracking analysis, by western blot for presence of tetraspanin CD63, CD81, annexin II, cythocrome C protein and, finally, by immunoelectron microscopy (IEM). Presence and quantitation of JCPyV-DNA were assessed with Multiplex real-time TaqMan PCR assay.
Results:
The JCPyV-DNA plasma prevalence in 120 HIV positive patients and 50 healthy donors was 28% and 4%, respectively. The investigation performed on well-characterized plasma EV reported JCPyV-DNA detection in 15 out of 36 (42%) of the viremic samples (14 were from HIV patients and 1 from healthy people) at a mean level of 23.5 copies/mL. The examination of EV selected samples reported the percentage of JCPyV-DNA in EV of 5.4% of the total viral load. Moreover, IEM reported the presence of JCPyV Vp1 antigen in plasma-derived EV.
Conclusion:
The potential role of EV-associated JCPyV-DNA open new avenues and mechanistic insights into the molecular strategies adopted by this polyomavirus to persist in the host and spread to the central nervous system.
Insights
JC polyomavirus (JCPyV) DNA was detected in extracellular vesicles (EV) from HIV patients at risk for progressive multifocal leukoencephalopathy (PML). This finding suggests EVs may play a role in JCPyV persistence and spread to the central nervous system.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in immunocompromised individuals.
- Viruses, including JCPyV, may utilize extracellular vesicles (EVs) for propagation.
Purpose of the Study:
- To determine if JCPyV-DNA is present in circulating plasma EVs from patients at risk for PML.
- To investigate the potential role of EVs in JCPyV infection and pathogenesis.
Main Methods:
- Plasma samples from 120 HIV-positive patients and 50 healthy donors were analyzed.
- Extracellular vesicles (EVs) were isolated and characterized.
- JCPyV-DNA presence and quantity were measured using Multiplex real-time TaqMan PCR.
- Immunoelectron microscopy (IEM) was used to detect JCPyV Vp1 antigen in EVs.
Main Results:
- JCPyV-DNA was detected in 28% of HIV-positive patients and 4% of healthy donors.
- JCPyV-DNA was found in 42% of characterized plasma EVs from viremic samples.
- IEM confirmed the presence of JCPyV Vp1 antigen within plasma-derived EVs.
Conclusions:
- Extracellular vesicles harbor JCPyV-DNA and JCPyV Vp1 antigen.
- EV-associated JCPyV-DNA may offer insights into viral persistence and neuroinvasion mechanisms.
- This study highlights a potential novel pathway for JCPyV dissemination.
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