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. 1994 Dec;68(12):7891–7899. doi: 10.1128/jvi.68.12.7891-7899.1994

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.

G Varior-Krishnan 1, M C Trescol-Biémont 1, D Naniche 1, C Rabourdin-Combe 1, D Gerlier 1
PMCID: PMC237251  PMID: 7966579

Abstract

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.

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Selected References

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  1. Adams E. M., Brown M. C., Nunge M., Krych M., Atkinson J. P. Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity. J Immunol. 1991 Nov 1;147(9):3005–3011. [PubMed] [Google Scholar]
  2. Calin-Laurens V., Forquet F., Lombard-Platet S., Bertolino P., Chrétien I., Trescol-Biémont M. C., Gerlier D., Rabourdin-Combe C. High efficiency of endogenous antigen presentation by MHC class II molecules. Int Immunol. 1992 Oct;4(10):1113–1121. doi: 10.1093/intimm/4.10.1113. [DOI] [PubMed] [Google Scholar]
  3. Calin-Laurens V., Forquet F., Mottez E., Kanellopoulos J., Godeau F., Kourilsky P., Gerlier D., Rabourdin-Combe C. Cytosolic targeting of hen egg lysozyme gives rise to a short-lived protein presented by class I but not class II major histocompatibility complex molecules. Eur J Immunol. 1991 Mar;21(3):761–769. doi: 10.1002/eji.1830210332. [DOI] [PubMed] [Google Scholar]
  4. Caras I. W., Weddell G. N., Davitz M. A., Nussenzweig V., Martin D. W., Jr Signal for attachment of a phospholipid membrane anchor in decay accelerating factor. Science. 1987 Nov 27;238(4831):1280–1283. doi: 10.1126/science.2446389. [DOI] [PubMed] [Google Scholar]
  5. Diamond D. C., Finberg R., Chaudhuri S., Sleckman B. P., Burakoff S. J. Human immunodeficiency virus infection is efficiently mediated by a glycolipid-anchored form of CD4. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5001–5005. doi: 10.1073/pnas.87.13.5001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunster L. M., Schneider-Schaulies J., Löffler S., Lankes W., Schwartz-Albiez R., Lottspeich F., ter Meulen V. Moesin: a cell membrane protein linked with susceptibility to measles virus infection. Virology. 1994 Jan;198(1):265–274. doi: 10.1006/viro.1994.1029. [DOI] [PubMed] [Google Scholar]
  7. Dörig R. E., Marcil A., Chopra A., Richardson C. D. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993 Oct 22;75(2):295–305. doi: 10.1016/0092-8674(93)80071-l. [DOI] [PubMed] [Google Scholar]
  8. Gerlier D., Garnier F., Forquet F. Haemagglutinin of measles virus: purification and storage with preservation of biological and immunological properties. J Gen Virol. 1988 Aug;69(Pt 8):2061–2069. doi: 10.1099/0022-1317-69-8-2061. [DOI] [PubMed] [Google Scholar]
  9. Gerlier D., Loveland B., Varior-Krishnan G., Thorley B., McKenzie I. F., Rabourdin-Combe C. Measles virus receptor properties are shared by several CD46 isoforms differing in extracellular regions and cytoplasmic tails. J Gen Virol. 1994 Sep;75(Pt 9):2163–2171. doi: 10.1099/0022-1317-75-9-2163. [DOI] [PubMed] [Google Scholar]
  10. Gerlier D., Trescol-Biémont M. C., Varior-Krishnan G., Naniche D., Fugier-Vivier I., Rabourdin-Combe C. Efficient MHC class II-restricted presentation of measles virus to T cells relies on its targeting to its cellular receptor human CD46 and involves an endosomal pathway. Cell Biol Int. 1994 May;18(5):315–320. doi: 10.1006/cbir.1994.1080. [DOI] [PubMed] [Google Scholar]
  11. Gerlier D., Trescol-Biémont M. C., Varior-Krishnan G., Naniche D., Fugier-Vivier I., Rabourdin-Combe C. Efficient major histocompatibility complex class II-restricted presentation of measles virus relies on hemagglutinin-mediated targeting to its cellular receptor human CD46 expressed by murine B cells. J Exp Med. 1994 Jan 1;179(1):353–358. doi: 10.1084/jem.179.1.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Germain R. N. MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation. Cell. 1994 Jan 28;76(2):287–299. doi: 10.1016/0092-8674(94)90336-0. [DOI] [PubMed] [Google Scholar]
  13. Harrowe G., Mitsuhashi M., Payan D. G. Measles virus-substance P receptor interactions. Possible novel mechanism of viral fusion. J Clin Invest. 1990 Apr;85(4):1324–1327. doi: 10.1172/JCI114571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Humbert M., Bertolino P., Forquet F., Rabourdin-Combe C., Gerlier D., Davoust J., Salamero J. Major histocompatibility complex class II-restricted presentation of secreted and endoplasmic reticulum resident antigens requires the invariant chains and is sensitive to lysosomotropic agents. Eur J Immunol. 1993 Dec;23(12):3167–3172. doi: 10.1002/eji.1830231219. [DOI] [PubMed] [Google Scholar]
  15. Jasin M., Page K. A., Littman D. R. Glycosylphosphatidylinositol-anchored CD4/Thy-1 chimeric molecules serve as human immunodeficiency virus receptors in human, but not mouse, cells and are modulated by gangliosides. J Virol. 1991 Jan;65(1):440–444. doi: 10.1128/jvi.65.1.440-444.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Keller G. A., Siegel M. W., Caras I. W. Endocytosis of glycophospholipid-anchored and transmembrane forms of CD4 by different endocytic pathways. EMBO J. 1992 Mar;11(3):863–874. doi: 10.1002/j.1460-2075.1992.tb05124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koike S., Ise I., Nomoto A. Functional domains of the poliovirus receptor. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4104–4108. doi: 10.1073/pnas.88.10.4104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lee J. D., Kravchenko V., Kirkland T. N., Han J., Mackman N., Moriarty A., Leturcq D., Tobias P. S., Ulevitch R. J. Glycosyl-phosphatidylinositol-anchored or integral membrane forms of CD14 mediate identical cellular responses to endotoxin. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9930–9934. doi: 10.1073/pnas.90.21.9930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Liszewski M. K., Post T. W., Atkinson J. P. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. doi: 10.1146/annurev.iy.09.040191.002243. [DOI] [PubMed] [Google Scholar]
  20. Lombard-Platlet S., Bertolino P., Deng H., Gerlier D., Rabourdin-Combe C. Inhibition by chloroquine of the class II major histocompatibility complex-restricted presentation of endogenous antigens varies according to the cellular origin of the antigen-presenting cells, the nature of the T-cell epitope, and the responding T cell. Immunology. 1993 Dec;80(4):566–573. [PMC free article] [PubMed] [Google Scholar]
  21. Lublin D. M., Atkinson J. P. Decay-accelerating factor and membrane cofactor protein. Curr Top Microbiol Immunol. 1990;153:123–145. doi: 10.1007/978-3-642-74977-3_7. [DOI] [PubMed] [Google Scholar]
  22. Lublin D. M., Coyne K. E. Phospholipid-anchored and transmembrane versions of either decay-accelerating factor or membrane cofactor protein show equal efficiency in protection from complement-mediated cell damage. J Exp Med. 1991 Jul 1;174(1):35–44. doi: 10.1084/jem.174.1.35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Manchester M., Liszewski M. K., Atkinson J. P., Oldstone M. B. Multiple isoforms of CD46 (membrane cofactor protein) serve as receptors for measles virus. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2161–2165. doi: 10.1073/pnas.91.6.2161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Medof M. E., Lublin D. M., Holers V. M., Ayers D. J., Getty R. R., Leykam J. F., Atkinson J. P., Tykocinski M. L. Cloning and characterization of cDNAs encoding the complete sequence of decay-accelerating factor of human complement. Proc Natl Acad Sci U S A. 1987 Apr;84(7):2007–2011. doi: 10.1073/pnas.84.7.2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Naniche D., Varior-Krishnan G., Cervoni F., Wild T. F., Rossi B., Rabourdin-Combe C., Gerlier D. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993 Oct;67(10):6025–6032. doi: 10.1128/jvi.67.10.6025-6032.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Naniche D., Wild T. F., Rabourdin-Combe C., Gerlier D. A monoclonal antibody recognizes a human cell surface glycoprotein involved in measles virus binding. J Gen Virol. 1992 Oct;73(Pt 10):2617–2624. doi: 10.1099/0022-1317-73-10-2617. [DOI] [PubMed] [Google Scholar]
  27. Naniche D., Wild T. F., Rabourdin-Combe C., Gerlier D. Measles virus haemagglutinin induces down-regulation of gp57/67, a molecule involved in virus binding. J Gen Virol. 1993 Jun;74(Pt 6):1073–1079. doi: 10.1099/0022-1317-74-6-1073. [DOI] [PubMed] [Google Scholar]
  28. Russell S. M., Sparrow R. L., McKenzie I. F., Purcell D. F. Tissue-specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing. Eur J Immunol. 1992 Jun;22(6):1513–1518. doi: 10.1002/eji.1830220625. [DOI] [PubMed] [Google Scholar]
  29. Selvaraj P., Carpén O., Hibbs M. L., Springer T. A. Natural killer cell and granulocyte Fc gamma receptor III (CD16) differ in membrane anchor and signal transduction. J Immunol. 1989 Nov 15;143(10):3283–3288. [PubMed] [Google Scholar]
  30. Shenoy-Scaria A. M., Kwong J., Fujita T., Olszowy M. W., Shaw A. S., Lublin D. M. Signal transduction through decay-accelerating factor. Interaction of glycosyl-phosphatidylinositol anchor and protein tyrosine kinases p56lck and p59fyn 1. J Immunol. 1992 Dec 1;149(11):3535–3541. [PubMed] [Google Scholar]
  31. Staunton D. E., Gaur A., Chan P. Y., Springer T. A. Internalization of a major group human rhinovirus does not require cytoplasmic or transmembrane domains of ICAM-1. J Immunol. 1992 May 15;148(10):3271–3274. [PubMed] [Google Scholar]
  32. Tremblay M., Meloche S., Gratton S., Wainberg M. A., Sékaly R. P. Association of p56lck with the cytoplasmic domain of CD4 modulates HIV-1 expression. EMBO J. 1994 Feb 15;13(4):774–783. doi: 10.1002/j.1460-2075.1994.tb06320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wild T. F., Malvoisin E., Buckland R. Measles virus: both the haemagglutinin and fusion glycoproteins are required for fusion. J Gen Virol. 1991 Feb;72(Pt 2):439–442. doi: 10.1099/0022-1317-72-2-439. [DOI] [PubMed] [Google Scholar]

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