Measles virus fusion machinery activated by sialic acid binding globular domain

Area of Science:

• Virology
• Molecular Biology
• Structural Biology

Background:

• Paramyxoviruses like measles virus (MV) and Newcastle disease virus (NDV) use viral envelope glycoproteins to fuse with host cells.
• Fusion is mediated by a receptor binding protein (H for MV, HN for NDV) and a fusion protein (F).
• MV's H protein binds protein receptors, while NDV's HN protein binds sialic acid receptors, with distinct proposed fusion activation mechanisms.

Purpose of the Study:

• To investigate the mechanism of paramyxovirus fusion activation.
• To determine if receptor binding domains of receptor binding proteins are interchangeable.
• To explore a unified mechanism of fusion activation within the Paramyxovirinae subfamily.

Main Methods:

• Constructed a chimeric protein combining the NDV HN receptor binding region with the MV H stalk domain.
• Engineered the NDV HN globular domain to bind a proteinaceous receptor.
• Assessed the ability of these engineered proteins to activate the MV F protein for cell fusion.

Main Results:

• A chimeric protein with NDV HN binding region and MV H stalk activated MV F-mediated fusion.
• Engineering the NDV HN globular domain to bind protein receptors retained fusion activation signaling.
• These findings suggest the receptor binding domain's interaction with the stalk is conserved.

Conclusions:

• The receptor binding domains of paramyxovirus receptor binding proteins are interchangeable.
• The stalk domain plays a crucial role in transmitting the fusion activation signal.
• A unified mechanism for fusion activation exists for the Paramyxovirinae subfamily, with conserved signaling pathways.