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Measles virus hemagglutinin: structural insights into cell entry and measles vaccine
Takao Hashiguchi1, Katsumi Maenaka, Yusuke Yanagi
1Department of Virology, Faculty of Medicine, Kyushu University Fukuoka, Japan.
Abstract:
Measles is one of the most contagious viral diseases, and remains a major cause of childhood morbidity and mortality worldwide. The measles virus (MV), a member of the family Paramyxoviridae, enters cells through a cellular receptor, the signaling lymphocyte activation molecule (SLAM), CD46 or nectin-4. Entry is mediated by two MV envelope glycoproteins, the hemagglutinin (H) and the fusion (F) protein. The H protein mediates receptor attachment, while the F protein causes membrane fusion. The interaction between the H and F proteins is essential to initiate the cell entry process. Recently determined crystal structures of the MV-H protein unbound and bound to SLAM or CD46 have provided insights into paramyxovirus entry and the effectiveness of measles vaccine.
Insights
Measles virus enters cells using hemagglutinin (H) and fusion (F) proteins. New crystal structures reveal how the H protein binds receptors, aiding measles vaccine development.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Measles virus (MV) is a highly contagious pathogen causing significant global childhood illness and death.
- MV entry into host cells is facilitated by its envelope glycoproteins: hemagglutinin (H) and fusion (F) protein.
- Cellular receptors targeted by MV include signaling lymphocyte activation molecule (SLAM), CD46, and nectin-4.
Purpose of the Study:
- To elucidate the structural mechanisms of MV entry into host cells.
- To understand the interaction between MV-H protein and its cellular receptors (SLAM, CD46).
- To provide insights relevant to the development and effectiveness of measles vaccines.
Main Methods:
- X-ray crystallography was employed to determine the structures of the MV-H protein.
- Structures were determined for both unbound MV-H protein and MV-H in complex with SLAM and CD46 receptors.
Main Results:
- Detailed crystal structures of the MV-H protein, both alone and bound to SLAM or CD46, were obtained.
- These structures illuminate the molecular details of receptor binding mediated by the H protein.
- The findings highlight the critical role of the H-F protein interaction in initiating MV cell entry.
Conclusions:
- Structural insights into MV-H protein-receptor interactions are crucial for understanding paramyxovirus entry mechanisms.
- This research provides a foundation for improving the efficacy of existing measles vaccines and developing novel antiviral strategies.
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