A single amino acid change in the cytoplasmic domains of measles virus glycoproteins H and F alters targeting, endocytosis, and cell fusion in polarized Madin-Darby canine kidney cells

As we have shown previously, release of measles virus (MV) from polarized e pithelial cells is not determined by the viral envelope proteins H and F, A lthough virus budding is restricted to the apical surfaces, both proteins w ere abundantly expressed on the basolateral surface of Madin-Darby canine k idney cells. In this report, we provide evidence that the basolateral expre ssion of the viral proteins is of biological importance for the MV infectio n of polarized epithelial cells. We demonstrate that both MV glycoproteins possess a basolateral targeting signal that is dependent upon the unique ty rosine in the cytoplasmic tails. These tyrosines are shown to be also part of an endocytosis signal. In MV-infected cells, internalization of the glyc oproteins was not observed, indicating that recognition of the endocytosis signals is disturbed by viral factors. In contrast, basolateral transport w as not substantially hindered, resulting in efficient cell-to-cell fusion o f polarized Madin-Darby canine kidney cells. Thus, recognition of the signa ls for endocytosis and polarized transport is differently regulated in infe cted cells. Mutation of the basolateral sorting signal in one of the MV gly coproteins prevented fusion of polarized cells. These results suggest that basolateral expression of the MV glycoproteins favors virus spread in epith elia.