gms | German Medical Science

The cell membrane predominantly contains phospholipids, sphingolipids and cholesterol. Sphingolipids and cholesterol spontaneously associate and separate from other phospholipids, which finally results in the formation of very small distinct membrane domains, named rafts. Rafts have been previously shown to be involved in the infection of human cells by several pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Neisseriae gonorrhoeae or HIV. However, it is unknown whether rhinoviruses also employ sphingomyelin-enriched membrane domains to infect human epithelial cells. Here, we demonstrate that infection of human nasal epithelial cells with several rhinovirus strains results in a re-organization of the cell membrane and the formation of large membrane platforms that were visualized employing the raft marker choleratoxin. Rhinoviruses localized to these membrane platforms. The significance of this finding is indicated by studies destroying membrane rafts employing the drugs beta-cyclodextrin, nystatin or filipin, respectively. These drugs prevented the infection of cultured or ex-vivo isolated nasal epithelial cells with rhinoviruses. Furthermore, rhinoviral infections induced an activation of tyrosine kinases and a re-organization of the cytoskeleton, events that were also prevented by destruction of membrane rafts. The data indicate that rhinoviruses infect human epithelial cells via rafts. Destruction of rafts efficiently prevents the infection and might be a novel approach for prevention or treatment of common cold.