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 epithelial cells is not determined by the viral envelope proteins H and F. Although virus budding is restricted to the apical surfaces, both proteins were abundantly expressed on the basolateral surface of Madin-Darby canine kidney cells. In this report, we provide evidence that the basolateral expression of the viral proteins is of biological importance for the MV infection of polarized epithelial cells. We demonstrate that both MV glycoproteins possess a basolateral targeting signal that is dependent upon the unique tyrosine in the cytoplasmic tails. These tyrosines are shown to be also part of an endocytosis signal. In MV-infected cells, internalization of the glycoproteins was not observed, indicating that recognition of the endocytosis signals is disturbed by viral factors. In contrast, basolateral transport was not substantially hindered, resulting in efficient cell-to-cell fusion of polarized Madin-Darby canine kidney cells. Thus, recognition of the signals for endocytosis and polarized transport is differently regulated in infected cells. Mutation of the basolateral sorting signal in one of the MV glycoproteins prevented fusion of polarized cells. These results suggest that basolateral expression of the MV glycoproteins favors virus spread in epithelia.
Moll
M
M
Institut für Virologie, Philipps-Universität Marburg, D-35037 Marburg, Germany.
Klenk
H D
HD
Herrler
G
G
Maisner
A
A
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004705:Endocytosis / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology*; D006389:Hemagglutinins, Viral / Q000502:physiology*; D008457:Measles / Q000473:pathology / Q000821:virology*; D008459:Measles virus / Q000502:physiology*; D008969:Molecular Sequence Data; D017354:Point Mutation; D014779:Virus Replication / Q000235:genetics
D006389:Hemagglutinins, Viral; C032397:hemagglutinin protein G, measles virus