Receptor concentration and diffusivity control multivalent binding of Sv40 to membrane bilayers

Area of Science:

• Virology
• Biophysics
• Cell Biology

Background:

• Simian Virus 40 (SV40) initiates infection by binding to the GM1 glycolipid receptor on the host cell plasma membrane.
• This binding induces membrane deformation, leading to endocytosis and subsequent viral infection.
• Efficient infection relies on receptor lipid structure and the arrangement of binding sites on the virus.

Purpose of the Study:

• To investigate the role of receptor diffusion, concentration, and the number of receptors required for stable Simian Virus 40 (SV40) binding.
• To elucidate the early events of virus attachment to lipid membranes at the nanoscopic level.
• To provide quantitative insights into virus-host interactions.

Main Methods:

• Computational modeling based on experimental data from supported membrane bilayers.
• Fluorescence correlation spectroscopy to measure SV40 virion diffusion rates.
• Single molecule tracking for receptor diffusion measurement.
• Quartz-crystal microbalance with dissipation (QCM-D) to quantify SV40 binding to GM1-containing bilayers.
• Development of a phenomenological stochastic dynamics model.

Main Results:

• SV40 requires a minimum of four bound GM1 receptors for stable attachment to the membrane.
• Receptor diffusion is essential for stable binding across physiological receptor concentrations.
• Receptor concentration dictates the mode of viral motion on the target membrane.
• Quantitative insights into the initial stages of virus-host interaction were obtained.

Conclusions:

• The study provides a quantitative understanding of the initial steps in SV40 infection.
• Receptor dynamics and concentration are critical factors governing viral attachment and entry.
• Findings highlight the importance of nanoscopic interactions in virus-host cell recognition.