Measles pp 111-127 | Cite as

Current Animal Models: Transgenic Animal Models for the Study of Measles Pathogenesis

  • C. I. Sellin
  • B. HorvatEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 330)

Animal models are highly important to understand the pathologic mechanisms of viral diseases. Therefore, the lack of a suitable animal model has greatly hindered the research into the pathogenesis of measles. Identification of two human receptors for measles virus, CD46 and CD150 (SLAM) has opened new perspectives in this field. During the last decade, numerous transgenic animal models have been developed in order to humanize mice and use them to study measles infection and virus—host interactions. Despite their limitations, these models have provided remarkable insights in different aspects of measles infection, providing a better understanding of virus-induced neuropathology, immunosuppression, mechanisms of virus virulence, and contribution of innate and adaptive immune response in viral clearance. They should certainly continue to help in studies of the host and viral factors that are important in measles infection and in developing of new antiviral agentsand measles virus-based vaccines. In addition, as CD46 serves as a receptor for two other human viruses, some of these models may also find an important application in the study of adenovirus and herpesvirus 6 infection. In this review, we describe different CD46 and CD150 transgenic models and detail their utilization in the study of various aspects of measles pathogenesis.


West Nile Virus Measle Virus Membrane Cofactor Protein Measle Virus Infection Signaling Lymphocytic Activation Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Andres O, Obojes K, Kim KS, ter Meulen V, Schneider-Schaulies J (2003) CD46- and CD150-inde-pendent endothelial cell infection with wild-type measles viruses. J Gen Virol 84:1189–1197PubMedCrossRefGoogle Scholar
  2. Blixenkrone-Moller M, Bernard A, Bencsik A, Sixt N, Diamond LE, Logan JS, Wild TF (1998) Role of CD46 in measles virus infection in CD46 transgenic mice. Virology 249:238–248PubMedCrossRefGoogle Scholar
  3. Cathomen T, Mrkic B, Spehner D, Drillien R, Naef R, Pavlovic J, Aguzzi A, Billeter MA, Cattaneo R (1998) A matrix-less measles virus is infectious and elicits extensive cell fusion:consequences for propagation in the brain. EMBO J 17:3899–3908PubMedCrossRefGoogle Scholar
  4. Christiansen D, Devaux P, Reveil B, Evlashev A, Horvat B, Lamy J, Rabourdin-Combe C, Cohen JH, Gerlier D (2000) Octamerization enables soluble CD46 receptor to neutralize measles virus in vitro and in vivo. J Virol 74:4672–4678PubMedCrossRefGoogle Scholar
  5. Combredet C, Labrousse V, Mollet L, Lorin C, Delebecque F, Hurtrel B, McClure H, Feinberg MB, Brahic M, Tangy F (2003) A molecularly cloned Schwarz strain of measles virus vaccine induces strong immune responses in macaques and transgenic mice. J Virol 77:11546–11554PubMedCrossRefGoogle Scholar
  6. Despres P, Combredet C, Frenkiel MP, Lorin C, Brahic M, Tangy F (2005) Live measles vaccine expressing the secreted form of the West Nile virus envelope glycoprotein protects against West Nile virus encephalitis. J Infect Dis 191:207–214PubMedCrossRefGoogle Scholar
  7. DiPaolo N, Ni S, Gaggar A, Strauss R, Tuve S, Li ZY, Stone D, Shayakhmetov D, Kiviat N, Toure P et al (2006) Evaluation of adenovirus vectors containing serotype 35 fibers for vaccination.Mol Ther 13:756–765PubMedCrossRefGoogle Scholar
  8. Dorig RE, Marcil A, Chopra A, Richardson CD (1993) The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75:295–305PubMedCrossRefGoogle Scholar
  9. Druelle J, Sellin CI, Waku-Kouomou D, Horvat B, Wild FT (2008) Wild type measles virus attenuation independent of type I IFN. Virol J 5:22PubMedCrossRefGoogle Scholar
  10. Evlashev A, Moyse E, Valentin H, Azocar O, Trescol-Biemont MC, Marie JC, Rabourdin-Combe C, Horvat B (2000) Productive measles virus brain infection and apoptosis in CD46 transgenic mice. J Virol 74:1373–1382PubMedCrossRefGoogle Scholar
  11. Evlashev A, Valentin H, Rivailler P, Azocar O, Rabourdin-Combe C, Horvat B (2001) Differential permissivity to measles virus infection of human and CD46-transgenic murine lymphocytes. J Gen Virol 82:2125–2129PubMedGoogle Scholar
  12. Gaggar A, Shayakhmetov DM, Lieber A (2003) CD46 is a cellular receptor for group B adenovi-ruses. Nat Med 9:1408–1412PubMedCrossRefGoogle Scholar
  13. Hahm B, Arbour N, Naniche D, Homann D, Manchester M, Oldstone MB (2003) Measles virus infects and suppresses proliferation of T lymphocytes from transgenic mice bearing human signaling lymphocytic activation molecule. J Virol 77:3505–3515PubMedCrossRefGoogle Scholar
  14. Hahm B, Arbour N, Oldstone MB (2004) Measles virus interacts with human SLAM receptor on dendritic cells to cause immunosuppression. Virology 323:292–302PubMedCrossRefGoogle Scholar
  15. Hahm B, Trifilo MJ, Zuniga EI, Oldstone MB (2005) Viruses evade the immune system through type I interferon-mediated STAT2-dependent but STAT1-independent signaling. Immunity 22:247–257PubMedCrossRefGoogle Scholar
  16. Hahm B, Cho JH, Oldstone MB (2007) Measles virus-dendritic cell interaction via SLAM inhibits innate immunity: selective signaling through TLR4 but not other TLRs mediates suppression of IL-12 synthesis. Virology 358:251–257PubMedCrossRefGoogle Scholar
  17. Hashimoto K, Ono N, Tatsuo H, Minagawa H, Takeda M, Takeuchi K, Yanagi Y (2002) SLAM (CD150)-independent measles virus entry as revealed by recombinant virus expressing green fluorescent protein. J Virol 76:6743–6749PubMedCrossRefGoogle Scholar
  18. Horvat B, Rivailler P, Varior-Krishnan G, Cardoso A, Gerlier D, Rabourdin-Combe C (1996) Transgenic mice expressing human measles virus (MV) receptor CD46 provide cells exhibiting different permissivities to MV infection. J Virol 70:6673–6681PubMedGoogle Scholar
  19. Kemper C, Leung M, Stephensen CB, Pinkert CA, Liszewski MK, Cattaneo R, Atkinson JP (2001) Membrane cofactor protein (MCP; CD46) expression in transgenic mice. Clin Exp Immunol 124:180–189PubMedCrossRefGoogle Scholar
  20. Kerdiles YM, Sellin CI, Druelle J, Horvat B (2006) Immunosuppression caused by measles virus: role of viral proteins. Rev Med Virol 16:49–63PubMedCrossRefGoogle Scholar
  21. Kouomou DW, Wild TF (2002) Adaptation of wild-type measles virus to tissue culture. J Virol 76:1505–1509PubMedGoogle Scholar
  22. Lawrence DM, Vaughn MM, Belman AR, Cole JS,Rall GF (1999) Immune response-mediated protection of adult but not neonatal mice from neuron-restricted measles virus infection and central nervous system disease. J Virol 73:1795–1801PubMedGoogle Scholar
  23. Lawrence DM, Patterson CE, Gales TL, D'Orazio JL, Vaughn MM, Rall GF (2000) Measles virus spread between neurons requires cell contact but not CD46 expression syncytium formation or extracellular virus production. J Virol 74:1908–1918PubMedCrossRefGoogle Scholar
  24. Lorin C, Mollet L, Delebecque F, Combredet C, Hurtrel B, Charneau P, Brahic M, Tangy F (2004)A single injection of recombinant measles virus vaccines expressing human immunodeficiency virus (HIV) type 1 clade B envelope glycoproteins induces neutralizing antibodies and cellular immune responses to HIV. J Virol 78:146–157PubMedCrossRefGoogle Scholar
  25. Makhortova NR, Askovich P, Patterson CE, Gechman LA, Gerard NP, Rall GF (2007) Neurokinin-1 enables measles virus trans-synaptic spread in neurons. Virology 362:235–244PubMedCrossRefGoogle Scholar
  26. Manchester M, Eto DS, Oldstone MB (1999) Characterization of the inflammatory response during acute measles encephalitis in NSE-CD46 transgenic mice. J Neuroimmunol 96:207–217PubMedCrossRefGoogle Scholar
  27. Marie JC, Kehren J, Trescol-Biemont MC, Evlashev A, Valentin H, Walzer T, Tedone R, Loveland B, Nicolas JF, Rabourdin-Combe C, Horvat B (2001) Mechanism of measles virus-induced suppression of inflammatory immune responses. Immunity 14:69–79PubMedCrossRefGoogle Scholar
  28. Marie JC, Astier AL, Rivailler P, Rabourdin-Combe C, Wild TF, Horvat B (2002) Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell induced inflammation. Nat Immunol 3:659–666PubMedGoogle Scholar
  29. Mrkic B, Pavlovic J, Rulicke T, Volpe P, Buchholz CJ, Hourcade D, Atkinson JP, Aguzzi A,Cattaneo R (1998) Measles virus spread and pathogenesis in genetically modified mice. J Virol 72:7420–7427PubMedGoogle Scholar
  30. Mrkic B, Odermatt B, Klein MA, Billeter MA, Pavlovic J, Cattaneo R (2000) Lymphatic dissemination and comparative pathology of recombinant measles viruses in genetically modified mice. J Virol 74:1364–1372PubMedCrossRefGoogle Scholar
  31. Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, Gerlier D (1993) Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus.J Virol 67:6025–6032PubMedGoogle Scholar
  32. Niewiesk S, Schneider-Schaulies J, Ohnimus H, Jassoy C, Schneider-Schaulies S, Diamond L,Logan JS, and ter Meulen V (1997) CD46 expression does not overcome the intracellular block of measles virus replication in transgenic rats. J Virol 71:7969–7973PubMedGoogle Scholar
  33. Ohno S, Ono N, Seki F, Takeda M, Kura S, Tsuzuki T, Yanagi Y (2007) Measles virus infection of SLAM (CD150) knockin mice reproduces tropism and immunosuppression in human infection. J Virol 81:1650–1659PubMedCrossRefGoogle Scholar
  34. Oldstone MB, Lewicki H, Thomas D, Tishon A, Dales S, Patterson J, Manchester M, Homann D,Naniche D, Holz A (1999) Measles virus infection in a transgenic model: virus-induced immu-nosuppression and central nervous system disease. Cell 98:629–640PubMedCrossRefGoogle Scholar
  35. Oldstone MB, Dales S, Tishon A, Lewicki H, Martin L (2005) A role for dual viral hits in causation of subacute sclerosing panencephalitis. J Exp Med 202:1185–1190PubMedCrossRefGoogle Scholar
  36. Ono N, Tatsuo H, Tanaka K, Minagawa H, Yanagi Y (2001) V domain of human SLAM (CDw150) is essential for its function as a measles virus receptor. J Virol 75:1594–1600PubMedCrossRefGoogle Scholar
  37. Patterson JB, Thomas D, Lewicki H, Billeter MA, Oldstone MB (2000) V and C proteins of measles virus function as virulence factors in vivo. Virology 267:80–89PubMedCrossRefGoogle Scholar
  38. Patterson JB, Cornu TI, Redwine J, Dales S, Lewicki H, Holz A, Thomas D, Billeter MA,Oldstone MB (2001) Evidence that the hypermutated M protein of a subacute sclerosing pan-encephalitis measles virus actively contributes to the chronic progressive CNS disease.Virology 291:215–225PubMedCrossRefGoogle Scholar
  39. Patterson CE, Lawrence DM, Echols LA, Rall GF (2002) Immune-mediated protection from measles virus-induced central nervous system disease is noncytolytic and gamma interferon dependent. J Virol 76:4497–4506PubMedCrossRefGoogle Scholar
  40. Patterson CE, Daley JK, Echols LA, Lane TE, Rall GF (2003) Measles virus infection induces chemokine synthesis by neurons. J Immunol 171:3102–3109PubMedGoogle Scholar
  41. Peng KW, TenEyck CJ, Galanis E, Kalli KR, Hartmann LC, Russell SJ (2002) Intraperitoneal therapy of ovarian cancer using an engineered measles virus. Cancer Res 62:4656–4662PubMedGoogle Scholar
  42. Rall GF, Manchester M, Daniels LR, Callahan EM, Belman AR, Oldstone MB (1997) A transgenic mouse model for measles virus infection of the brain. Proc Natl Acad Sci U S A 94:4659–4663PubMedCrossRefGoogle Scholar
  43. Rivailler P, Trescol-Biemont MC, Gimenez C, Rabourdin-Combe C, Horvat B (1998) Enhanced MHC class II-restricted presentation of measles virus (MV) hemagglutinin in transgenic mice expressing human MV receptor CD46. Eur J Immunol 28:1301–1314PubMedCrossRefGoogle Scholar
  44. Roscic-Mrkic Schwendener Odermatt B, Zuniga A, Pavlovic J, Billeter MA, Cattaneo R (2001) Roles of macrophages in measles virus infection of genetically modified mice. J Virol 75:3343–3351PubMedCrossRefGoogle Scholar
  45. Santoro F, Kennedy PE, Locatelli G, Malnati MS, Berger EA, Lusso P (1999) CD46 is a cellular receptor for human herpesvirus 6. Cell 99:817–827PubMedCrossRefGoogle Scholar
  46. Sellin CI, Davoust N, Guillaume V, Baas D, Belin MF, Buckland R, Wild TF, Horvat B (2006) High pathogenicity of wild-type measles virus infection in CD150 (SLAM) transgenic mice. J Virol 80:6420–6429PubMedCrossRefGoogle Scholar
  47. Shingai M, Inoue N, Okuno T, Okabe M, Akazawa T, Miyamoto Y, Ayata M, Honda K, Kurita-Taniguchi M, Matsumoto M et al (2005) Wild-type measles virus infection in human CD46/CD150-transgenic mice: CD11c-positive dendritic cells establish systemic viral infection. J Immunol 175:3252–3261PubMedGoogle Scholar
  48. Slifka MK, Homann D, Tishon A, Pagarigan R, Oldstone MB (2003) Measles virus infection results in suppression of both innate and adaptive immune responses to secondary bacterial infection. J Clin Invest 111:805–810PubMedGoogle Scholar
  49. Takeuchi K, Miyajima N, Nagata N, Takeda M, Tashiro M (2003) Wild-type measles virus induces large syncytium formation in primary human small airway epithelial cells by a SLAM(CD150)-independent mechanism. Virus Res 94:11–16PubMedCrossRefGoogle Scholar
  50. Tatsuo H, Ono N, Tanaka K, Yanagi Y (2000) SLAM (CDw150) is a cellular receptor for measles virus. Nature 406:893–897PubMedCrossRefGoogle Scholar
  51. Thorley BR, Milland J, Christiansen D, Lanteri MB, McInnes B, Moeller I, Rivailler P, Horvat B,Rabourdin-Combe C, Gerlier D et al (1997) Transgenic expression of a CD46 (membrane cofactor protein) minigene: studies of xenotransplantation and measles virus infection. Eur J Immunol 27:726–734PubMedCrossRefGoogle Scholar
  52. Tishon A, Lewicki H, Andaya A, McGavern D, Martin L, Oldstone MB (2006) CD4 T cell control primary measles virus infection of the CNS: regulation is dependent on combined activity with either CD8 T cells or with B cells: CD4 CD8 or B cells alone are ineffective. Virology 347:234–245PubMedCrossRefGoogle Scholar
  53. Welstead GG, Iorio C, Draker R, Bayani J, Squire J, Vongpunsawad S, Cattaneo R, Richardson CD (2005) Measles virus replication in lymphatic cells and organs of CD150 (SLAM) trans-genic mice. Proc Natl Acad Sci U S A 102:16415–16420PubMedCrossRefGoogle Scholar
  54. WHO (2002) Scaling up the response to infectious Cited 26 May 2008
  55. Yannoutsos N, Ijzermans JN, Harkes C, Bonthuis F, Zhou CY, White D, Marquet RL, Grosveld F (1996) A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection. Genes Cells 1:409–419+PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.U758-ENS LyonLyon Cedex 07France

Personalised recommendations