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Updated: Jun 10, 2026
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
Identification of key residues in virulent canine distemper virus hemagglutinin that control CD150/SLAM-binding
Ljerka Zipperle1, Johannes P M Langedijk, Claes Orvell
1Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Abstract:
Morbillivirus cell entry is controlled by hemagglutinin (H), an envelope-anchored viral glycoprotein determining interaction with multiple host cell surface receptors. Subsequent to virus-receptor attachment, H is thought to transduce a signal triggering the viral fusion glycoprotein, which in turn drives virus-cell fusion activity. Cell entry through the universal morbillivirus receptor CD150/SLAM was reported to depend on two nearby microdomains located within the hemagglutinin. Here, we provide evidence that three key residues in the virulent canine distemper virus A75/17 H protein (Y525, D526, and R529), clustering at the rim of a large recessed groove created by beta-propeller blades 4 and 5, control SLAM-binding activity without drastically modulating protein surface expression or SLAM-independent F triggering.
Insights
Specific residues on the morbillivirus hemagglutinin (H) protein control binding to the CD150/SLAM receptor. This finding is crucial for understanding morbillivirus cell entry mechanisms.
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Morbillivirus cell entry relies on the hemagglutinin (H) glycoprotein, which mediates host cell receptor interactions.
- H is believed to signal the viral fusion (F) glycoprotein to initiate virus-cell fusion after receptor binding.
- Previous studies suggested microdomains within H are critical for CD150/SLAM-mediated entry.
Purpose of the Study:
- To investigate the role of specific residues in the canine distemper virus H protein concerning CD150/SLAM receptor binding.
- To elucidate the molecular determinants of morbillivirus-host cell interactions.
Main Methods:
- Site-directed mutagenesis of key residues in the canine distemper virus A75/17 H protein.
- Analysis of SLAM-binding activity.
- Assessment of viral protein surface expression and SLAM-independent F triggering.
Main Results:
- Three specific residues (Y525, D526, R529) in the H protein were identified as critical for SLAM binding.
- These residues are located in a recessed groove formed by beta-propeller blades 4 and 5.
- Modifications at these sites did not significantly affect H surface expression or SLAM-independent F triggering.
Conclusions:
- The identified residues are essential for mediating CD150/SLAM receptor recognition by morbillivirus H.
- This provides a refined understanding of the molecular mechanisms governing morbillivirus cell entry.
- The findings may inform strategies for controlling morbillivirus infections.
