A truncated RARà co-operates with the v-erbB oncogene to transform early haematopoietic progenitors in vitro and in vivo

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Transgenic mice expressing human measles virus (MV) receptor CD46 provide cells exhibiting different permissivities to MV infections.

We have generated transgenic mice ubiquitously expressing the human receptor for measles virus (MV), CD46 (membrane cofactor protein). Various cell types were isolated from these transgenic mice and analyzed for their ability to support MV replication in vitro. Although MV could enter into all CD46-expressing cells, differential susceptibilities to MV infection were detected depending on the cell type. Cell cultures obtained from transgenic lungs and kidneys were found to be permissive of MV infection, since RNA specific for MV genes was detected and viral particles were released, although at a low level. Similarly to human lymphocytes, activated T and B lymphocytes isolated from transgenic mice could support MV replication; virus could enter, transcribe viral RNA, and produce new infectious particles. When expressing viral proteins, lymphocytes down-regulated CD46 from the surface. Interestingly, while activated T lymphocytes from nontransgenic mice did not support MV infection, activated nontransgenic murine B lymphocytes replicated MV as well as transgenic B lymphocytes, suggesting the use of an alternative virus receptor for entry. In contrast to the previous cell types, murine peritoneal and bone marrow-derived macrophages, regardless of whether they were activated, could not support MV replication. Furthermore, although MV entered into macrophages and virus-specific RNA transcription occurred, no virus protein or infectious virus particles could be detected. These results show the importance of the particular cell-type-specific host factors for MV replication in murine cells which may be responsible for the differential permissivity of MV infection

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.

International audienceThe 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

Measles virus receptor properties are shared by several CD46 isoforms differing in extracellular regions and cytoplasmic tails

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Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus.

A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) binding to host cells was previously used to characterize a 57- to 67-kDa cell surface glycoprotein as a potential MV receptor. In the present work, this glycoprotein (gp57/67) was immunopurified, and N-terminal amino acid sequencing identified it as human membrane cofactor protein (CD46), a member of the regulators of complement activation gene cluster. Transfection of nonpermissive murine cells with a recombinant expression vector containing CD46 cDNA conferred three major properties expected of cells permissive to MV infection. First, expression of CD46 enabled MV to bind to murine cells. Second, the CD46-expressing murine cells were able to undergo cell-cell fusion when both MV hemagglutinin and MV fusion glycoproteins were expressed after infection with a vaccinia virus recombinant encoding both MV glycoproteins. Third, M12.CD46 murine B cells were able to support MV replication, as shown by production of infectious virus and by cell biosynthesis of viral hemagglutinin after metabolic labeling of infected cells with [35S]methionine. These results show that the human CD46 molecule serves as an MV receptor allowing virus-cell binding, fusion, and viral replication and open new perspectives in the study of MV pathogenesis