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JC virus infection in cells from lymphoid tissue
M C Monaco1, J Shin, E O Major
1Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Abstract:
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease characterized by infection of oligodendrocytes by JC virus. The exact nature of the pathogenesis of PML is not known. The nature of the primary infection, the site of viral latency, and the route by which JCV enters the brain remain to be elucidated. Different laboratories have shown the presence of JCV in peripheral lymphocytes from immunosuppressed individuals, suggesting these cells as possible carriers of JCV to the brain. To examine this observation, we tested the susceptibility to JCV infection of cells from lymphoid organs, focusing our attention on CD34+ haematopoietic precursor cells and B lymphocytes. The results demonstrate that both these cell types are susceptible to JCV infection and, moreover, that JCV can infect only those cells that differentiate into lymphocytic lineage.
Insights
JC virus (JCV) infects immune cells, specifically CD34+ hematopoietic precursor cells and B lymphocytes. These cells may serve as carriers for JCV to the brain, contributing to progressive multifocal leukoencephalopathy (PML) pathogenesis.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes.
- The precise mechanisms of JCV pathogenesis, including primary infection sites and brain entry routes, are not fully understood.
- JCV presence in peripheral lymphocytes of immunosuppressed individuals suggests a potential role for these cells in viral dissemination to the central nervous system.
Purpose of the Study:
- To investigate the susceptibility of lymphoid organ cells, particularly CD34+ hematopoietic precursor cells and B lymphocytes, to JCV infection.
- To determine if lymphocytes can act as carriers for JCV to the brain, elucidating a potential route for PML development.
Main Methods:
- In vitro infection assays were performed on primary human CD34+ hematopoietic precursor cells and B lymphocytes.
- Flow cytometry and immunofluorescence microscopy were used to detect JCV infection and cellular differentiation markers.
Main Results:
- Both CD34+ hematopoietic precursor cells and B lymphocytes demonstrated susceptibility to JCV infection.
- JCV infection was observed specifically in cells undergoing differentiation towards a lymphocytic lineage.
- These findings support the hypothesis that lymphocytes can be infected by JCV.
Conclusions:
- CD34+ hematopoietic precursor cells and B lymphocytes are susceptible to JCV infection.
- JCV preferentially infects differentiating lymphocytic lineage cells, suggesting a mechanism for viral transport to the brain.
- This study provides critical insights into the cellular tropism of JCV and potential pathways for PML pathogenesis.