GLYCOSYL-PHOSPHATIDYLINOSITOL-ANCHORED AND TRANSMEMBRANE FORMS OF CD46 DISPLAY SIMILAR MEASLES-VIRUS RECEPTOR PROPERTIES - VIRUS BINDING, FUSION, AND REPLICATION DOWN-REGULATION BY HEMAGGLUTININ AND VIRUS UPTAKE AND ENDOCYTOSIS FOR ANTIGEN PRESENTATION BY MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II MOLECULES

The CD46 molecule is a receptor for measles virus (MV), CD46, which pr otects autologous cells from complement-mediated damage, exists in sev eral isoforms which are variably expressed in different human tissues, These isoforms differ in their cytoplasmic and transmembrane regions and in a small portion of their proximal extracytoplasmic regions. To examine the role of the cytoplasmic and transmembrane regions of CD46 in MV infection, mouse M12 B cells stably expressing a transmembrane o r a chimeric glycosylphosphatidylinositol (GPI)-anchored form of CD46 (CD46-GPI) were used. Both the GPI-anchored and transmembrane CD46 for ms were able to mediate MV binding. MV binding mediated by the GPI-anc hored form but not that mediated by the transmembrane form was abolish ed after treatment with phosphatidylinositol phospholipase C. MV infec tion of both M12.CD46 and M12.CD46-GPI cells but not parental M12 cell s resulted in MV replication. Expression of hemagglutinin induced cell surface down-regulation of both CD46 and CD46-GPI. Both M12.CD46 and M12.CD46-GPI cells were able to efficiently capture MV for presentatio n of viral antigens by major histocompatibility complex class II molec ules to T cells. This presentation was blocked by chloroquine, indicat ing some virus endocytosis. These data imply that the extracytoplasmic region encompassing the four N-terminal invariable short consensus re peat regions of CD46 is sufficient to act as a receptor for MV and tha t the cytoplasmic and transmembrane regions of CD46 may not play a maj or role in the signal for the hemagglutinin-induced down-regulation of CD46 and/or endocytosis of MV.