Affinity thresholds for membrane fusion triggering by viral glycoproteins

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• Enveloped viruses utilize membrane fusion for cellular entry.
• Attachment protein receptor affinities vary widely (10^-4 M to 10^-9 M), but their functional significance remains unclear.

Purpose of the Study:

• To investigate the impact of varying receptor affinities on viral attachment, infectivity, and cell-cell fusion.
• To determine if higher receptor affinities beyond a certain threshold offer additional benefits.

Main Methods:

• Engineering six retargeted measles viruses with a 5-log range of affinities for the Her-2/neu receptor.
• Assessing viral attachment, infectivity, and intercellular fusion efficiencies across different affinity levels.

Main Results:

• Receptor affinity had minimal impact on initial viral attachment to cells.
• A distinct affinity threshold was identified, above which efficient cell-cell fusion occurred.
• Viral infectivity and intercellular fusion were significantly influenced by receptor affinity.

Conclusions:

• Receptor affinity is a critical determinant of viral infectivity and membrane fusion efficiency, not merely attachment.
• An affinity threshold exists for efficient viral-mediated cell-cell fusion.
• Suprathreshold receptor affinities do not enhance fusion efficiency further.