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 protects autologous cells from complement-mediated damage, exists in several 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 or a chimeric glycosyl-phosphatidylinositol (GPI)-anchored form of CD46 (CD46-GPI) were used. Both the GPI-anchored and transmembrane CD46 forms were able to mediate MV binding. MV binding mediated by the GPI-anchored form but not that mediated by the transmembrane form was abolished after treatment with phosphatidylinositol phospholipase C. MV infection of both M12.CD46 and M12.CD46-GPI cells but not parental M12 cells 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 presentation of viral antigens by major histocompatibility complex class II molecules to T cells. This presentation was blocked by chloroquine, indicating some virus endocytosis. These data imply that the extracytoplasmic region encompassing the four N-terminal invariable short consensus repeat regions of CD46 is sufficient to act as a receptor for MV and that the cytoplasmic and transmembrane regions of CD46 may not play a major role in the signal for the hemagglutinin-induced down-regulation of CD46 and/or endocytosis of MV.
Varior-Krishnan
G
G
Centre National de la Recherche Scientifique-ENS UMR 49, Lyon, France.
Trescol-Biémont
M C
MC
Naniche
D
D
Rabourdin-Combe
C
C
Gerlier
D
D
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D001402:B-Lymphocytes; D002460:Cell Line; D015536:Down-Regulation; D005434:Flow Cytometry; D017261:Glycosylphosphatidylinositols / Q000502:physiology*; D006388:Hemagglutinins / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D011991:Receptors, Virus / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014779:Virus Replication
D015703:Antigens, CD; C497857:CD46 protein, human; D017261:Glycosylphosphatidylinositols; D006388:Hemagglutinins; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins