ADAPTATION OF MEASLES-VIRUS TO POLARIZED EPITHELIAL-CELLS - ALTERATIONS IN VIRUS ENTRY AND RELEASE

We have previously shown that the Edmonston strain of measles virus en ters and is released preferentially at the apical surfaces of polarize d epithelial cells. Small amounts of virus were found to be released a t the basal surface. In the present study, we passaged the virus in po larized cells and characterized the passaged virus for its pattern of entry and release in epithelial cells as well as the ability to downre gulate the receptor CD46. In contrast to the original stock virus, the passaged virus was found to be released at close to the same levels f rom both the apical and the basal surfaces. Accumulation of viral nucl eocapsids and virus budding were observed at both membrane surfaces wh en cells were infected with the passaged virus. The passaged virus was also found to enter efficiently at the basal surface, unlike the orig inal stock virus. Syncytial formation was observed at earlier times po stinfection in cells infected with the passaged virus compared to cell s infected with the stock virus. On Caco-2 cells, CD46 is found on bot h 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 o n the basolateral membrane of Caco-2 cells, while the passaged Edmonst on measles virus did not downregulate CD46 on either surface. These da ta indicate that passage of measles virus through polarized epithelial cells results in selection of virus which exhibits a bidirectional pa ttern of entry and release through both the apical and the basolateral surfaces and which no longer downregulates CD46 expression on the cel l surface. (C) 1997 Academic Press.