Viral cell recognition and entry

Area of Science:

• Virology
• Structural Biology
• Drug Discovery

Background:

• Rhinovirus infection begins with cell-surface receptor recognition.
• Major rhinovirus serotypes utilize intercellular adhesion molecule-1 (ICAM-1) for attachment.
• Viral attachment triggers conformational changes leading to genomic RNA release.

Purpose of the Study:

• To structurally characterize the interaction between rhinovirus and its cellular receptor.
• To identify potential drug-binding sites for inhibiting viral entry.
• To elucidate the role of the "pocket factor" in viral uncoating and RNA release.

Main Methods:

• X-ray crystallography and sequence comparisons to predict the receptor binding site.
• Electron microscopy of human rhinovirus 14 (HRV14) and HRV16 complexed with ICAM-1.
• Analysis of hydrophobic drug compound binding within a pocket beneath the viral canyon.

Main Results:

• Electron microscopy confirmed the canyon as the ICAM-1 binding site on HRV14 and HRV16.
• A hydrophobic pocket adjacent to the canyon binds inhibitory drug compounds.
• This pocket also binds an unidentified "pocket factor," overlapping the ICAM-1 binding site.

Conclusions:

• The viral canyon is the primary binding site for intercellular adhesion molecule-1 (ICAM-1).
• Drug compounds binding to a hydrophobic pocket can inhibit rhinovirus attachment and uncoating.
• Competition between the pocket factor and ICAM-1 at the binding site regulates viral RNA entry into the cell.