Specificity of Morbillivirus Hemagglutinins to Recognize SLAM of Different Species

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Measles virus (MV) and canine distemper virus (CDV) are morbilliviruses with significant public health and veterinary implications.
• Morbillivirus hemagglutinin (H) protein mediates cell entry by binding to signaling lymphocyte activation molecule (SLAM) receptors, influencing host tropism and range.
• Understanding receptor-binding specificities is crucial due to concerns about potential host range expansion of morbilliviruses.

Purpose of the Study:

• To investigate and compare the receptor-binding potential of morbillivirus H proteins from different species.
• To elucidate the molecular basis of H protein specificity for SLAM receptors across various hosts.
• To assess the implications of H-SLAM interactions for potential morbillivirus host expansion.

Main Methods:

• Binding assays were performed to evaluate the interaction of CDV-H and MV-H proteins with SLAM receptors from different species (human, dog, tamarin, mouse).
• Fusion assays, guided by the structural data of the MV-H-SLAM complex, were employed to study receptor specificity.
• Mutagenesis studies were conducted to identify key residues involved in H-SLAM interactions.

Main Results:

• CDV-H specifically binds to dog SLAM but not to human, tamarin, or mouse SLAM.
• MV-H binds to human, tamarin, and dog SLAM, but not to mouse SLAM.
• MV-H exhibited lower binding affinity and faster kinetics to dog SLAM compared to human SLAM, with similar viral entry efficiency in Vero cells expressing either receptor. Mutagenesis revealed differential tolerance for receptor specificity between MV-H and CDV-H.

Conclusions:

• The H protein of CDV and MV display distinct species-specificities for SLAM receptors.
• Differences in H-SLAM binding and tolerance for specificity suggest varying potentials for host adaptation and expansion.
• These findings provide critical insights into the molecular mechanisms governing morbillivirus host tropism and evolution.