Human rhinovirus 14 enters rhabdomyosarcoma cells expressing icam-1 by a clathrin-, caveolin-, and flotillin-independent pathway.
Intercellular adhesion molecule 1 (ICAM-1) mediates binding and entry of major group human rhinoviruses (HRVs). Whereas the entry pathway of minor group HRVs has been studied in detail and is comparatively well understood, the pathway taken by major group HRVs is largely unknown. Use of immunofluorescence microscopy, colocalization with specific endocytic markers, dominant negative mutants, and pharmacological inhibitors allowed us to demonstrate that the major group virus HRV14 enters rhabdomyosarcoma cells transfected to express human ICAM-1 in a clathrin-, caveolin-, and flotillin-independent manner. Electron microscopy revealed that many virions accumulated in long tubular structures, easily distinguishable from clathrin-coated pits and caveolae. Virus entry was strongly sensitive to the Na(+)/H(+) ion exchange inhibitor amiloride and moderately sensitive to cytochalasin D. Thus, cellular uptake of HRV14 occurs via a pathway exhibiting some, but not all, characteristics of macropinocytosis and is similar to that recently described for adenovirus 3 entry via alpha(v) integrin/CD46 in HeLa cells.
Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, Dr. Bohr Gasse 9/3, A-1030 Vienna, Austria.
Abdul Ghafoor
AG
Khan
Angela
A
Pickl-Herk
Leszek
L
Gajdzik
Thomas C
TC
Marlovits
Renate
R
Fuchs
Dieter
D
Blaas
D000584:Amiloride / Q000494:pharmacology; D022461:Caveolins / Q000378:metabolism; D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D032342:Muscle Cells / Q000821:virology*; D012229:Rhinovirus / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D053586:Virus Internalization
D022461:Caveolins; D002966:Clathrin; D008565:Membrane Proteins; D026941:Sodium Channel Blockers; C106354:flotillins; D018799:Intercellular Adhesion Molecule-1; D015638:Cytochalasin D; D000584:Amiloride