Human rhinovirus selectively modulates membranous and soluble forms of its intercellular adhesion molecule-1 (ICAM-1) receptor to promote epithelial cell infectivity.
Human rhinoviruses are responsible for many upper respiratory tract infections. 90% of rhinoviruses utilize intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, which also plays a critical role in recruitment of immune effector cells. Two forms of this receptor exist; membrane-bound (mICAM-1) and soluble ICAM-1 (sICAM-1). The soluble receptor may be produced independently from the membrane-bound form or it may be the product of proteolytic cleavage of mICAM-1. The ratio of airway epithelial cell expression of mICAM-1 to the sICAM-1 form may influence cell infectivity and outcome of rhinovirus infection. We therefore investigated the effect of rhinovirus on expression of both ICAM-1 receptors in normal human bronchial epithelial cells. We observed separate distinct messenger RNA transcripts coding for mICAM-1 and sICAM-1 in these cells, which were modulated by virus. Rhinovirus induced mICAM-1 expression on epithelial cells while simultaneously down-regulating sICAM-1 release, with consequent increase in target cell infectivity. The role of protein tyrosine kinases was investigated as a potential mechanistic pathway. Rhinovirus infection induced rapid phosphorylation of intracellular tyrosine kinase, which may be critical in up-regulation of mICAM-1. Elucidation of the underlying molecular mechanisms involved in differential modulation of both ICAM-1 receptors may lead to novel therapeutic strategies.
Whiteman
Suzanne C
SC
Lung Injury and Inflammation Research, Directorate of Respiratory Medicine, North Staffordshire Hospital Trust, Stoke-on-Trent ST4 6QG, United Kingdom. med16_2000@yahoo.com
Bianco
Andrea
A
Knight
Richard A
RA
Spiteri
Monica A
MA
D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000821:virology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000378:metabolism / Q000821:virology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000821:virology*; D012229:Rhinovirus / Q000378:metabolism / Q000472:pathogenicity*; D012995:Solubility; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D003609:Dactinomycin; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases