Droplet-based single-cell pairing for high-throughput interaction mapping of antigen-receptor combinations.

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Understanding viral antigen and human receptor interactions is key for predicting disease susceptibility.
• Viral mutations and human genetic variations significantly impact infection risk.

Purpose of the Study:

• To develop a high-throughput system for profiling interactions between viral variants and human cell receptors.
• To analyze how genetic variations influence susceptibility to viral infections.

Main Methods:

• Developed a droplet-based single-cell pairing and library-on-library interaction screening (SPLIS) system.
• Used droplet sorting and merging to pair sender and receiver cells.
• Sequenced DNA readouts to characterize syncytium-formation potential of variant combinations.

Main Results:

• Characterized fusion-enhancing and -inhibiting variant pairs.
• Profiled how ACE2 single-nucleotide polymorphisms affect susceptibility to SARS-CoV-2 spike mutations.
• Demonstrated the system's ability to interrogate interactions between variant libraries.

Conclusions:

• The SPLIS system provides valuable insights into host susceptibility and viral infectivity.
• This technology aids in understanding host-pathogen interactions at a molecular level.
• Informs precision public health strategies by predicting infection susceptibility.