MEASLES-VIRUS RECEPTOR PROPERTIES ARE SHARED BY SEVERAL CD46 ISOFORMSDIFFERING IN EXTRACELLULAR REGIONS AND CYTOPLASMIC TAILS

Human CD46, a member of the family of regulators of complement activat ion, 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-expres sed in all tissues except erythrocytes. The optional exons encode extr acellular serine-, threonine- and proline-rich regions of CD46 (design ated STP-A, -B and -C) which are located proximal to the plasma membra ne, and alternative cytoplasmic tails (CYT1 or CYT2). The ability of t he BC-CYT2, B-CYT2 and BC-CYT1 CD46 isoforms, expressed in rodent Chin ese hamster ovary (CHO) cells, to mediate MV infection was tested. Eve ry isoform was recognized by a monoclonal antibody (MAb), MCI20.6, whi ch recognizes the MV-binding site on CD46. CHO cells expressing any of these CD46 isoforms were able to bind MV, the level of binding correl ating with the CD46 expression level. Likewise, MV infection induced t he cell-cell fusion of all CD46-expressing CHO cells but not of the pa rental CHO cells. Accordingly, MV replication was observed after infec tion of CHO cells expressing each CD46 isoform but not after infection of parental CHO cells. Finally, cell surface expression of every isof orm was decreased after infection by MV. Altogether these data showed that the specific STP regions of CD46 played no major role in HA-media ted MV binding to CD46, virus infection and virus-induced down-regulat ion of CD46. Moreover, the CYT1 and CYT2 cytoplasmic tails of CD46 are either functionally similar although having distinct amino acid seque nces or are dispensable for interaction with HA of MV.