Functional and structural interactions between measles virus hemagglutinin and CD46

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Measles virus (MV) and canine distemper virus (CDV) are morbilliviruses that utilize cell surface receptors for entry.
• Human CD46 serves as the primary receptor for MV.
• The roles of MV surface glycoproteins, hemagglutinin (H) and fusion (F), in receptor interaction and cell fusion are not fully elucidated.

Purpose of the Study:

• To analyze the specific roles of MV H and F glycoproteins in functional and structural interactions with human CD46.
• To determine which glycoprotein dictates MV fusion specificity and CD46 dependence.
• To compare the interaction and specificity of MV glycoproteins with those of CDV.

Main Methods:

• Recombinant vaccinia virus vectors were used to express MV and CDV H and F glycoproteins in cell populations.
• Cell-cell fusion assays, including reporter gene activation and syncytium formation, were employed.
• Flow cytometry and antibody coprecipitation were used to assess glycoprotein-receptor interactions.

Main Results:

• MV glycoproteins mediated fusion with primate cells but not nonprimate cells, unless CD46 was present.
• CDV glycoproteins mediated fusion with both primate and nonprimate cells independently of CD46.
• The H glycoprotein, not F, determined the fusion specificity for both MV and CDV, with MV H specifically interacting with CD46.

Conclusions:

• The measles virus hemagglutinin (H) glycoprotein is critical for determining MV specificity for CD46-positive cells.
• A direct functional and structural interaction exists between MV H and human CD46.
• Fusion specificity in morbilliviruses is dictated by the H glycoprotein, highlighting its role in host range and entry.