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Interaction of CD46 with measles virus: accessory role of CD46 short consensus repeat IV
D Christiansen1, B Loveland, P Kyriakou
1Immunité et Infections Virales, IVMC, CNRS-UCBL UMR 5537, 69372 Lyon Cedex 08, France The Austin Research Institute, Heidelberg, Victoria 3084, Australia. christia@laennec.univ-lyon1.fr
Abstract:
To define further the accessory role(s) of the CD46 (membrane cofactor protein) short consensus repeat (SCR) III and IV domains in the interaction of CD46 with measles virus (MV), chimeric proteins were generated by substituting domains from the structurally related protein decay accelerating factor (DAF, CD55): x3DAF (exchange of CD46 SCR III) and x4DAF (exchange of SCR IV). Transfected CHO cell lines that stably expressed these chimeric proteins were compared for MV binding and infection. Compared with wild-type CD46 (I-II-III-IV), a significant decrease in MV binding was observed with x4DAF. Despite this limited binding, these cells were still capable of supporting virus entry. In a quantitative fusion assay, no significant differences in fusion were observed as a result of the exchange of either CD46 SCR III or IV. However, the down-regulation of cell surface CD46 typically observed following MV infection was abolished with x4DAF, as was the redistribution of CD46 on the cell surface. Thus, CD46 SCR IV appears to be required for optimal virus binding and receptor down-regulation, although importantly, in spite of these functional limitations, x4DAF can still be used for MV entry.
Insights
The CD46 protein
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- CD46 acts as a receptor for measles virus (MV).
- The short consensus repeat (SCR) domains of CD46 play roles in MV interaction.
- CD46's SCR III and IV domains are investigated for their accessory functions.
Purpose of the Study:
- To elucidate the specific roles of CD46 SCR III and IV domains in measles virus binding and infection.
- To generate and analyze chimeric proteins involving CD46 and decay accelerating factor (DAF).
Main Methods:
- Generation of chimeric proteins by exchanging CD46 SCR III (x3DAF) and SCR IV (x4DAF) with DAF domains.
- Comparison of MV binding, entry, and fusion in transfected Chinese Hamster Ovary (CHO) cells expressing wild-type CD46 and chimeric proteins.
- Assessment of MV-induced CD46 down-regulation and redistribution on the cell surface.
Main Results:
- x4DAF showed significantly reduced MV binding compared to wild-type CD46.
- Despite reduced binding, x4DAF-expressing cells supported MV entry.
- No significant differences in fusion were observed between chimeric and wild-type proteins.
- MV-induced down-regulation and redistribution of CD46 were abolished in x4DAF-expressing cells.
Conclusions:
- CD46 SCR IV is crucial for optimal measles virus binding and receptor down-regulation.
- The CD46 SCR IV domain is essential for MV-induced CD46 surface changes.
- Measles virus can still enter cells via the x4DAF chimeric protein, indicating partial functionality.