Measles virus receptor properties are shared by several CD46 isoforms differing in extracellular regions and cytoplasmic tails.
Human CD46, a member of the family of regulators of complement activation, has been shown recently to act as a measles virus (MV) receptor, interacting with the virus envelope glycoprotein haemagglutinin (HA). Owing to alternative RNA splicing, several CD46 isoforms are co-expressed in all tissues except erythrocytes. The optional exons encode extracellular serine-, threonine- and proline-rich regions of CD46 (designated STP-A, -B and -C) which are located proximal to the plasma membrane, and alternatively cytoplasmic tails (CYT1 or CYT2). The ability of the BC-CYT2, B-CYT2 and BC-CYT1 CD46 isoforms, expressed in rodent Chinese hamster ovary (CHO) cells, to mediate MV infection was tested. Every isoform was recognized by a monoclonal antibody (MAb), MCI20.6, which recognizes the MV-binding site on CD46. CHO cells expressing any of these CD46 isoforms were able to bind MV, the level of binding correlating with the CD46 expression level. Likewise, MV infection induced the cell-cell fusion of all CD46-expressing CHO cells but not of the parental CHO cells. Accordingly, MV replication was observed after infection of CHO cells expressing each CD46 isoform but not after infection of parental CHO cells. Finally, cell surface expression of every isoform was decreased after infection by MV. Altogether these data showed that the specific STP regions of CD46 played no major role in HA-mediated MV binding to CD46, virus infection and virus-induced down-regulation of CD46. Moreover, the CYT1 and CYT2 cytoplasmic tails of CD46 are either functionally similar although having distinct amino acid sequences or are dispensable for interaction with HA of MV.
Gerlier
D
D
Immunobiologie Moléculaire, CNRS-ENS UMR 49, Lyon, France.
Loveland
B
B
Varior-Krishnan
G
G
Thorley
B
B
McKenzie
I F
IF
Rabourdin-Combe
C
C
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D016466:CHO Cells; D002462:Cell Membrane / Q000276:immunology; D006224:Cricetinae; D005434:Flow Cytometry; D014644:Genetic Variation; D006801:Humans; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D014162:Transfection; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins