Adaptation of measles virus to polarized epithelial cells: Alterations in virus entry and release

Abstract

We have previously shown that the Edmonston strain of measles virus enters and is released preferentially at the apical surfaces of polarized epithelial cells. Small amounts of virus were found to be released at the basal surface. In the present study, we passaged the virus in polarized cells and characterized the passaged virus for its pattern of entry and release in epithelial cells as well as the ability to downregulate the receptor CD46. In contrast to the original stock virus, the passaged virus was found to be released at close to the same levels from both the apical and the basal surfaces. Accumulation of viral nucleocapsids and virus budding were observed at both membrane surfaces when cells were infected with the passaged virus. The passaged virus was also found to enter efficiently at the basal surface, unlike the original stock virus. Syncytial formation was observed at earlier times postinfection in cells infected with the passaged virus compared to cells infected with the stock virus. On Caco-2 cells, CD46 is found on both surfaces but is preferentially expressed on the apical membrane. The original Edmonston stock and two other wild-type strains, Chicago and Davis, were found to downregulate CD46 levels on the apical but not on the basolateral membrane of Caco-2 cells, while the passaged Edmonston measles virus did not downregulate CD46 on either surface. These data indicate that passage of measles virus through polarized epithelial cells results in selection of virus which exhibits a bidirectional pattern of entry and release through both the apical and the basolateral surfaces and which no longer downregulates CD46 expression on the cell surface.