INFECTION OF A POLARIZED EPITHELIAL-CELL LINE WITH WILD-TYPE REOVIRUS LEADS TO VIRUS PERSISTENCE AND ALTERED CELLULAR FUNCTION

The mechanisms and consequences of persistence of non-transforming viruses are poorly understood. Reovirus infections are usually regarded as cytocidal and infection is associated with inhibition of cellular protein and DNA synthesis. Reovirus infection of the polarized epithelial MDCK cell line is not associated with inhibition of protein synthesis, and cells become persistently infected and continue to grow without c.p.e. after infection. After several passages, virus persistence is associated with profound morphological and functional changes. The cells lose their usual cobblestone appearance and acquire a fibroblastic, undifferentiated morphology. This is associated with an inability to form tight junctions. In addition, expression of epidermal growth factor receptors and one adhesion protein is altered in the persistently infected cells. These results demonstrate that reovirus persistence will occur readily, and that infection of differentiated cells with a non-transforming virus can lead to loss of differentiation and abnormal protein expression.