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Selective expression of a subset of measles virus receptor-competent CD46 isoforms in human brain
C J Buchholz1, D Gerlier, A Hu
1Institut fur Molekularbiologie, Abteilung I, Hönggerberg, Universität, Zürich, Switzerland.
Abstract:
The human cell surface protein CD46 is the main measles virus (MV) receptor. We analyzed the CD46 isoforms expressed in the brain of three patients who died with persistent MV infections and in an unaffected brain. Complete CD46 cDNAs were produced and found to code exclusively for CD46 isoforms with cytoplasmic tail 2. Selective expression of tail 2 isoforms was shown in a second control brain by Western blots with antibodies specific for each of the cytoplasmic tails. Binding of purified MV particles and virus-dependent cell fusion were tested after transient expression of brain-derived CD46 proteins in mouse cells. All the brain-derived proteins mediated MV binding and virus-dependent fusion. Isoforms containing both serine/threonine/proline (STP)-rich domains were more active in virus binding, whereas isoforms with only one STP domain were more efficient in mediating fusion.
Insights
Measles virus (MV) uses the CD46 protein as its primary receptor. Brain cells from persistent MV infections exclusively express CD46 isoforms with cytoplasmic tail 2, which mediate MV binding and fusion.
Area of Science:
- Virology
- Cell Biology
- Neuroscience
Background:
- The human cell surface protein CD46 serves as the primary receptor for measles virus (MV).
- Understanding CD46 isoform expression in the brain is crucial for persistent MV infections.
Purpose of the Study:
- To analyze CD46 isoforms in the brain of patients with persistent MV infections.
- To investigate the functional role of brain-derived CD46 isoforms in MV binding and fusion.
Main Methods:
- Analysis of complete CD46 cDNAs from patient brains.
- Western blot analysis using tail-specific antibodies.
- Transient expression of CD46 proteins in mouse cells for functional assays.
Main Results:
- CD46 isoforms with cytoplasmic tail 2 were exclusively found in brains with persistent MV infections.
- Brain-derived CD46 proteins effectively mediated MV binding and virus-dependent cell fusion.
- Isoforms with two STP-rich domains showed higher MV binding activity, while those with one STP domain were more efficient in cell fusion.
Conclusions:
- Cytoplasmic tail 2 CD46 isoforms are selectively expressed in the brain during persistent MV infections.
- These specific CD46 isoforms play a significant role in mediating MV entry and pathogenesis in the central nervous system.