1887

Abstract

We have shown previously that basolateral targeting of plasmid-encoded measles virus (MV) F and H protein is dependent on single tyrosine residues in the cytoplasmic tails of the glycoproteins and is essential for fusion activity in polarized epithelial cells. Here, we present data on the functional importance of polarized glycoprotein expression for the cytopathic properties of infectious MV in culture and for pathogenesis . By the introduction of single point mutations, we generated recombinant viruses in which the basolateral targeting signal of either one or both glycoproteins was destroyed (tyrosine mutants). As a consequence, the mutated glycoproteins were predominantly expressed on the apical membrane of polarized Madin–Darby canine kidney cells. In contrast to parental MV, none of these virus mutants was able to spread by syncytia formation in polarized cells showing that the presence of both MV glycoproteins at the basolateral cell surface is required for cell-to-cell fusion . Using cotton rats as an animal model that allows MV replication in the respiratory tract, we showed that basolateral glycoprotein targeting is also of importance for the spread of infection . Whereas parental MV was able to spread laterally within the respiratory epithelium and from there to cells in the underlying tissue, tyrosine mutants infected only single epithelial and very few subepithelial cells. These data strongly suggest that basolateral targeting of MV glycoproteins helps to overcome the epithelial barrier and thereby facilitates the systemic spread of MV infection .

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2004-04-01
2019-11-12
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