Discrimination among rhinovirus serotypes for a variant ICAM-1 receptor molecule

Area of Science:

• Structural biology
• Virology
• Immunology

Background:

• Intercellular adhesion molecule 1 (ICAM-1) serves as the cellular receptor for major human rhinovirus (HRV) serotypes.
• Naturally occurring ICAM-1 variants, like ICAM-1Kilifi, exhibit altered binding affinities for different HRV serotypes.

Purpose of the Study:

• To elucidate the structural basis for differential binding of HRV14 and HRV16 to ICAM-1 and its variant, ICAM-1Kilifi.
• To understand how variations in receptor-virus interactions affect binding stability and specificity.

Main Methods:

• Cryo-electron microscopy (cryoEM) image reconstruction determined the 3D structures of HRV-ICAM-1 and HRV-ICAM-1Kilifi complexes.
• X-ray crystallography structures of viruses and ICAM-1 were fitted into cryoEM density maps.
• Analysis of ionic networks and salt bridges at the virus-receptor interfaces.

Main Results:

• HRV14 binds ICAM-1 transiently but stably to ICAM-1Kilifi; HRV16 binds ICAM-1 stably but not ICAM-1Kilifi.
• Virus-receptor interfaces feature extensive ionic networks, with ICAM-1Kilifi complexes having one less salt bridge than ICAM-1 complexes.
• The reduced salt bridge in ICAM-1Kilifi complexes disproportionately affects HRV16 binding due to its inherently fewer interactions with ICAM-1.

Conclusions:

• Structural differences in ICAM-1 and its variant ICAM-1Kilifi dictate differential binding of HRV serotypes.
• The number and nature of ionic interactions at the interface are critical for the stability and specificity of HRV-receptor complexes.
• Understanding these molecular interactions provides insights into viral entry mechanisms and host-pathogen dynamics.