Human rhinovirus selectively modulates membranous and soluble forms of its intercellular adhesion molecule-1 (ICAM-1) receptor to promote epithelial cell infectivity

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Human rhinoviruses cause frequent upper respiratory tract infections.
• Intercellular adhesion molecule-1 (ICAM-1) is a key receptor for 90% of rhinoviruses and mediates immune cell recruitment.
• ICAM-1 exists in membrane-bound (mICAM-1) and soluble (sICAM-1) forms, with their ratio potentially affecting rhinovirus infection outcomes.

Purpose of the Study:

• To investigate the effect of rhinovirus infection on the expression of both mICAM-1 and sICAM-1 in normal human bronchial epithelial cells.
• To explore the molecular mechanisms, including protein tyrosine kinases, underlying the differential regulation of ICAM-1 forms by rhinovirus.

Main Methods:

• Analysis of separate messenger RNA (mRNA) transcripts for mICAM-1 and sICAM-1 in bronchial epithelial cells.
• Assessment of rhinovirus-induced changes in mICAM-1 expression and sICAM-1 release.
• Investigation of protein tyrosine kinase phosphorylation following rhinovirus infection.

Main Results:

• Rhinovirus infection modulated distinct mRNA transcripts for mICAM-1 and sICAM-1.
• Virus exposure upregulated epithelial mICAM-1 expression while downregulating sICAM-1 release.
• Rhinovirus infection triggered rapid intracellular tyrosine kinase phosphorylation, potentially driving mICAM-1 upregulation.
• The observed changes led to increased target cell infectivity.

Conclusions:

• Rhinovirus differentially regulates mICAM-1 and sICAM-1 expression in airway epithelial cells.
• Upregulation of mICAM-1 and downregulation of sICAM-1 by rhinovirus contribute to increased viral infectivity.
• Protein tyrosine kinases play a role in the rhinovirus-mediated upregulation of mICAM-1.
• Understanding these mechanisms may reveal novel therapeutic strategies for rhinovirus infections.