Structure of a human rhinovirus complexed with its receptor molecule

Area of Science:

• Structural Biology
• Virology
• Immunology

Background:

• Understanding virus-receptor interactions is crucial for developing antiviral therapies.
• Human rhinoviruses are a major cause of the common cold, utilizing specific cellular receptors for entry.
• Previous predictions suggested viral attachment sites are located in antibody-inaccessible regions.

Purpose of the Study:

• To determine the high-resolution structure of human rhinovirus 16 complexed with its cellular receptor, intercellular adhesion molecule 1 (ICAM-1).
• To structurally validate the proposed model of viral attachment within a surface cavity.
• To investigate the atomic basis of virus-receptor recognition.

Main Methods:

• Cryoelectron microscopy was employed to visualize the virus-receptor complex.
• Computational modeling and analysis were used to interpret the electron density maps.
• Comparison with homologous structures (human rhinovirus 14 and CD4) was performed.

Main Results:

• The structure revealed that ICAM-1 binds within a deep 'canyon' on the surface of human rhinovirus 16.
• This binding site is approximately 12-Å deep, confirming its inaccessibility to host antibodies.
• Atomic structures of homologous viral and receptor components showed high correspondence, validating the observed interactions.

Conclusions:

• The study provides direct structural evidence for the location of the viral attachment site in a protected cavity.
• This confirms the hypothesis that viruses exploit antibody-resistant sites for cellular receptor binding.
• The findings offer insights into the molecular mechanisms of rhinovirus infection and potential therapeutic targets.