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Published on: February 11, 2015
CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell-cell fusion
Riccardo Cassiani-Ingoni1, Heather L Greenstone, Donatella Donati
1Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Membrane cofactor protein (CD46) is a regulator of complement activation that also serves as the entry receptor for human herpes virus 6 (HHV-6) and measles virus (MV) into human cells. While it is clear that oligodendrocytes and astrocytes are cell types commonly infected by these viruses, it is unclear whether oligodendrocytes express CD46, or which are the cellular mechanisms underlying the infection. We show that adult oligodendrocytes, as well as astrocytes and microglial cells, express CD46 on the cellular surface. Moreover, we employed a quantitative fusion assay to demonstrate that HHV-6A infection of T lymphocytes enables cell-cell fusion of these cells to astrocytes or to oligodendroglial cells. This fusion is mediated by the interaction between viral glycoproteins expressed on the membrane of the infected cells and CD46 on the glial targets, and is also observed using cells expressing recombinant MV glycoproteins. These data suggest a mechanism that involves cell-cell fusion by which certain viruses could spread the infection from the periphery to the cells in the nervous system.
Insights
Oligodendrocytes express CD46, a complement regulator and viral entry receptor. This enables virus-infected cells to fuse with glial cells, potentially spreading infection within the nervous system.
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Membrane cofactor protein (CD46) regulates complement and acts as an entry receptor for human herpesvirus 6 (HHV-6) and measles virus (MV).
- Oligodendrocytes and astrocytes are known targets of HHV-6 and MV, but CD46 expression and infection mechanisms in oligodendrocytes remain unclear.
Purpose of the Study:
- To investigate CD46 expression in oligodendrocytes and other glial cells.
- To elucidate the cellular mechanisms of HHV-6 and MV infection in the central nervous system.
Main Methods:
- Immunofluorescence to detect CD46 expression on oligodendrocytes, astrocytes, and microglial cells.
- Quantitative fusion assays using HHV-6A-infected T lymphocytes and cells expressing recombinant MV glycoproteins.
Main Results:
- Adult oligodendrocytes, astrocytes, and microglial cells express CD46 on their surface.
- HHV-6A infection facilitated cell-cell fusion between infected T lymphocytes and glial cells (astrocytes and oligodendrocytes).
- This fusion was mediated by viral glycoproteins interacting with CD46 on glial cells, and was also observed with MV glycoproteins.
Conclusions:
- Oligodendrocytes express CD46, serving as a potential entry receptor for HHV-6 and MV.
- Virus-mediated cell-cell fusion involving CD46 presents a mechanism for viral spread from peripheral cells to the central nervous system.
- This finding has implications for understanding neuroinflammation and viral pathogenesis in the brain.
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