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Cell entry by measles virus: long hybrid receptors uncouple binding from membrane fusion
C J Buchholz1, U Schneider, P Devaux
1Institut für Molekularbiologie, Universität Zürich, Switzerland.
Abstract:
The pH-independent fusion of membranes induced by measles virus (MV) requires, in addition to the fusion-competent protein F, hemagglutinin (H), and on the target membrane, the virus receptor CD46. We constructed hybrid receptors composed of different numbers and combinations of the four CD46 short consensus repeat (SCR) domains, followed by immunoglobulin-like domains of another cell surface protein, CD4. Hybrid proteins containing SCRs I and II bound MV particles and conferred fusion competence to rodent cells. SCRs III and/or IV strengthened MV binding. Increasing the distance between the MV binding site and the transmembrane domain enhanced virus binding but reduced fusion efficiency. A hybrid protein predicted to be about 120 Angstroms (12 nm) longer than the standard receptor lost fusion support function and was dominant negative over a functional receptor. These data indicate that receptor protein length influences virus binding and determines fusion efficiency.
Insights
The length of the measles virus (MV) receptor CD46 influences viral binding and membrane fusion. Specific domains (SCRs I and II) are crucial for MV attachment and cell fusion.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Measles virus (MV) membrane fusion is pH-independent.
- This process requires the viral fusion protein (F), hemagglutinin (H), and the CD46 receptor on target cells.
Purpose of the Study:
- To investigate the role of CD46 short consensus repeat (SCR) domains in MV binding and fusion.
- To determine how receptor length affects MV-host cell interactions.
Main Methods:
- Construction of hybrid CD46 receptors with varying SCR domain combinations.
- Testing MV binding and fusion competence in rodent cells expressing hybrid receptors.
- Analysis of receptor length effects on viral attachment and fusion efficiency.
Main Results:
- Hybrid receptors with SCRs I and II enabled MV binding and fusion.
- SCRs III and/or IV enhanced MV binding.
- Increased receptor length improved binding but reduced fusion efficiency, with excessively long receptors inhibiting fusion.
Conclusions:
- The length of the CD46 receptor is a critical determinant of measles virus fusion efficiency.
- Specific SCR domains mediate MV binding, while overall receptor length modulates the fusion process.