Pathogenic aspects of measles virus infections

  • S. Schneider-Schaulies
  • V. ter Meulen
Part of the Archives of Virology. Supplementa book series (ARCHIVES SUPPL, volume 15)


Measles virus (MV) infections normally cause an acute self limiting disease which is resumed by a virus-specific immune response and leads to the establishment of a lifelong immunity. Complications associated with acute measles can, on rare occasions, involve the central nervous system (CNS). These are postinfectious measles encephalitis which develops soon after infection, and, months to years after the acute disease, measles inclusion body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE) which are based on a persistent MV infection of brain cells. Before the advent of HIV, SSPE was the best studied slow viral infection of the CNS, and particular restrictions of MV gene expression as well as MV interactions with neural cells have revealed important insights into the pathogenesis of persistent viral CNS infections. MV CNS complication do, however, not large contribute to the high rate of mortality seen in association with acute measles worldwide. The latter is due to a virus-induced suppression of immune functions which favors the establishment of opportunistic infections. Mechanisms underlying MV-mediated immunosup- pression are not well understood. Recent studies have indicated that MV-induced disruption of immune functions may be multifactorial including the interference with cytokine synthesis, the induction of soluble inhibitory factors or apoptosis and negative signalling to T cells by the viral glycoproteins expressed on the surface of infected cells, particularly dendritic cells.


Measle Virus Subacute Sclerosing Panencephalitis Measle Virus Infection Measle Virus Strain Acute Measle 
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. 1.
    Arneborn P, Biberfeld G (1983) T-Lymphocyte subpopulations in relation to immuno-suppression in measles and varicella. Infect Immun 39: 29–37PubMedGoogle Scholar
  2. 2.
    Auwaerter P, Kaneshima H, McCune JM, Wiegand G, Griffin DE (1996) measles virus infection of thymic epithelium in the scid-hu mouse leads to thymocyte apoptosis. J Virol 70: 3 734–3 740Google Scholar
  3. 3.
    Baczko K, Pardowitz J, Rima BK, ter Meulen V (1992) Constant and variable regions of measles virus proteins encoded by the nucleocapsid and phosphoprotein genes derived from lytic and persistent viruses. Virology 190: 469–474PubMedCrossRefGoogle Scholar
  4. 4.
    Baczko K, Lampe J, Liebert UG, Brinckmann U, ter Meulen V, Pardowitz J, Budka H, Cosby SL, Isserte S, Rima BK (1993) Clonal expansion of hypermutated measles virus in a SSPE brain. Virology 197: 188–195PubMedCrossRefGoogle Scholar
  5. 5.
    Baczko K, Liebert UG, Billeter MA, Cattaneo R, Budka H, ter Meulen V (1986) Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis. J Virol 59: 472–478PubMedGoogle Scholar
  6. 6.
    Barrett PN, Koschel K, Carter M, ter Meulen V (1985) Effect of measles virus antibodies on a measles SSPE virus persistently infected C6 rat-glioma cell line. J Gen Virol 66: 1411–1421PubMedCrossRefGoogle Scholar
  7. 7.
    Bartz R, Brinckmann UG, Dunster LM, Rima BK, ter Meulen V, Schneider-Schaulies J (1996) Mapping amino acids of the measles virus haemagglutinin responsible for receptor (CD46) downregulation. Virology 224: 334–337PubMedCrossRefGoogle Scholar
  8. 8.
    Bartz R, Firsching R, Rima BK, ter Meulen V, Schneider-Schaulies J (1998) Differential receptor usage by measles virus strains. J Gen Virol 79: 1 015–1 025Google Scholar
  9. 9.
    Billeter MA, Cattaneo R, Spielhofer P, Kaelin K, Huber M, Schmid A, Baczko K, ter Meulen V (1994) Generation and properties of measles virus mutations typically associated with subacute sclerosing panencephalitis. Ann NY Acad Sci 724: 367–377PubMedCrossRefGoogle Scholar
  10. 10.
    Borrow P, Oldstone MBA (1995) Measles virus-mononuclear cell interactions. Curr Topics Microbiol Immunol 191: 85–100CrossRefGoogle Scholar
  11. 11.
    Buchholz CJ, Gerlier D, Hu A, Cathomen T, Liszewski MK, Atkinson JP, Cattaneo R (1995) Selective expression of a subset of measles virus receptor competent CD46 isoforms in human brain. Virology 217: 349–355CrossRefGoogle Scholar
  12. 12.
    Cattaneo R, Rebmann G, Schmid A, Baczko K, ter Meulen V, Billeter MA (1987) Altered transcription of a defective measles virus genome derived from a diseased human brain. EMBO J 6: 681–687PubMedGoogle Scholar
  13. 13.
    Cattaneo R, Rebmann G, Baczko K, ter Meulen V, Billeter MA (1987) Altered ratios of measles virus transcripts in diseased human brains. Virology 160: 523–526PubMedCrossRefGoogle Scholar
  14. 14.
    Cattaneo R, Rose JK (1993) Cell fusion by the envelope glycoproteins of persistent measles viruses which caused lethal human brain diseases. J Virol 67: 1493–1 502PubMedGoogle Scholar
  15. 15.
    Cattaneo R, Schmid A, Eschle D, Baczko K, ter Meulen V, Billeter MA (1988) Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell 55: 255–265PubMedCrossRefGoogle Scholar
  16. 16.
    Doerig RE, Marcil A, Chopra A, Richardson CD (1993) The human CD46 Molecule is a receptor for measles virus (Edmonston Strain). Cell 75: 295–305CrossRefGoogle Scholar
  17. 17.
    Dunster LM, Schneider-Schaulies J, Löffler S, Lankes W, Schwarz-Albiez R, Lottspeich F, ter Meulen V (1994) Moesin: A cell membrane protein linked with suceptibility to measles virus infection. Virology 198: 265–274PubMedCrossRefGoogle Scholar
  18. 18.
    Dunster LM, Schneider-Schaulies J, Dehoff MH, Holers VM, Schwartz-Albiez R, ter Meulen V (1995) Moesin, and not the murine functional homologue (crry/p65) of human membrane cofactor protein (CD46) is involved in the entry of measles virus (strain Edmonston) into susceptible murine cell lines. J Gen Virol 76: 2085–2089PubMedCrossRefGoogle Scholar
  19. 19.
    Ecker A, ter Meulen V, Baczko K, Schneider-Schaulies S (1995) MV-specific dsRNAs are targets for unwinding modifying activity in vitro. J Neurovirol 1: 92–100PubMedCrossRefGoogle Scholar
  20. 20.
    Esolen LM, Ward BJ, Moench TR, Griffin DE (1993) Infection of monocytes during measles. J Infect Dis 168: 47–52PubMedCrossRefGoogle Scholar
  21. 21.
    Esolen LE, Park SW, Hardwick JM, Griffin DE (1995) Apoptosis as a cause of death in measles virus-infected cells. J Virol 69: 3 955–3 958Google Scholar
  22. 22.
    Galama JMD, Ubels-Postma J, Vos A, Lucas CJ (1980) Measles virus inhibits acquisition of lymphocyte functions but not established effector functions. Cell Immunol 50: 405–415PubMedCrossRefGoogle Scholar
  23. 23.
    Fugier-Vivier I, Servet-Delprat C, Rivailler P, Riossan MC, Liu YJ, Rabourdin-Combe C (1997) Measles virus suprresses cell-mediated immunity by interfering with the survival and function of dendritic and T cells. J Exp Med 186: 813–823PubMedCrossRefGoogle Scholar
  24. 24.
    Griffin DE (1995) Immune responses during measles virus infecation. Curr Topics Microbiol Immunol 191: 117–134CrossRefGoogle Scholar
  25. 25.
    Grosjean I, Caux C, Bella C, Berger D, Wild TF, Banchereau J, Kaiserlian D (1997) Measles virus infects human dendritic cells and blocks their allostimulatory properties for CD4+ T cells. J Exp Med 186: 801–812PubMedCrossRefGoogle Scholar
  26. 26.
    Horikami S, Moyer SA (1995) Double stranded RNA adenosine deaminase activity during measles virus infection. Virus Res 36: 87–96PubMedCrossRefGoogle Scholar
  27. 27.
    Horikami S, Moyer SA (1995) Structure, transcription and replication of measles virus. Curr Topics Microbiol Immunol 191: 35–50CrossRefGoogle Scholar
  28. 28.
    Hsu EC, Sarangi F, Iorio C, Sidhu MS, Udem SA, Dillehay DL, Xu W, Rota PA, Bellini WJ, Richardson CD (1998) A single amino acid change in the haemagglutinin protein of measles virus determines its ability to bind CD46 and reveals another receptor on marmoset B cells. J Virol 72: 2 905–2 916Google Scholar
  29. 29.
    Johnstone RW, Loveland B, Mckenzie IFC (1993) Identification and quantification of complement regulator CD46 on normal human tissues. Immunology 79: 341–347PubMedGoogle Scholar
  30. 30.
    Karp CL, Wysocka M, Wahl LM, Ahearn JM, Cuomo PJ, Sherry B, Trinchieri G, Griffin DE (1996) Mechanism of suppression of cell-mediated immunity by measles virus. Science 273: 228–231PubMedCrossRefGoogle Scholar
  31. 31.
    Katz M (1995) Clinical spectrum of measles. Current Top Microbiol Immunol 191: 1–13CrossRefGoogle Scholar
  32. 32.
    Krantic S, Giminez C, Rabourdin-Combe C (1995) Cell-to-cell contact via measles virus haemagglutinin-CD46 interaction triggers CD46 downregulation. J Gen Virol 76: 2 793–2 800CrossRefGoogle Scholar
  33. 33.
    Komase K, Rima BK, Pardowitz J, Kunz C, BilleterMA, ter Meulen V, Baczko K (1995) A comparison of nucleotide sequences of measles virus L genes derived from wild type viruses and SSPE brain tissues. Virology 208: 795–799PubMedCrossRefGoogle Scholar
  34. 34.
    Kraus E, Schneider-Schaulies S, Miyasaka M, Tamatani T, Sedgwick J (1992) Augmentation of major histocompatibility complex class I and ICAM-1 expression on glial cells following measles virus infecation: evidence for the role of type-1 interferon. Eur J Immunol 22: 175–182PubMedCrossRefGoogle Scholar
  35. 35.
    Lecouturier V, Fayolle J, Caballero M, Carabana J, Celma ML, Fernandez-Munoz R, Wild TF, Buckland R (1996) Identification of two acids in the haemagglutinin glyco-protein of measles virus (MV) that govern hemadsorption, Hela cell fusion and CD46 downregulation: phenotypic markers that differentiate vaccine and wild-type MV strains. J Virol 70: 4 200–4 204Google Scholar
  36. 36.
    Liebert UG, Baczko K, Budka H, ter Meulen V (1986) Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis. J Gen Virol 67: 2435–2444PubMedCrossRefGoogle Scholar
  37. 37.
    Liebert UG, Schneider-Schaulies S, Baczko K, ter Meulen V (1990) Antibody-induced restriction of viral gene expression in measles encephalitis in rats. J Virol 64: 706–713PubMedGoogle Scholar
  38. 38.
    McChesney MB, Kehrl JH, Valsamakis A, Fauci AS, Oldstone MBA (1987) Measles virus infection of B lymphocytes permits cellular activation but blocks progression through the cell cycle. J Virol 61: 3 441–3 447Google Scholar
  39. 39.
    ter Meulen V, Stephenson JR, Kreth HW (1983) Subacute sclerosing panencephalitis. In: Fraenkel-Conrat H, Wagner RR (eds) Comprehensive virology. Elsevier, Amsterdam, pp 105–159Google Scholar
  40. 40.
    Nakayama T, Mori T, Yamaguchi S, Sonoda S, Asamura A, Yamashita R, Takeuchi Y, Urano T (1995) Detection of measles virus genome directly from clinical samples by reverse transcriptase-polymerase chain reaction and genetic variability. Virus Res 35: 1–16PubMedCrossRefGoogle Scholar
  41. 41.
    Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, Gerlier D (1993) Human membrane cofactor protein (CD46) acts a cellular receptor for measles virus. J Virol 67: 6 025–6 032Google Scholar
  42. 42.
    Niewiesk S, Schneider-Schaulies J, Ohnimus H, Jassoy C, Schneider-Schaulies S, Diamond L, Logan JS, 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
  43. 43.
    Niewiesk S, Eisenhuth I, Fooks A, Clegg JC, Schnorr JJ, Schneider-Schaulies S, ter Meulen V (1997) Measles virus induced immune suppression in the cotton rat (Sigmodon hispidus) model depends on viral glycoproteins. J Virol 71: 7 214–7 219Google Scholar
  44. 44.
    Nussbaum O, Broder CC, Moss B, Stern B, Rozenblatt S, Berger EA (1995) Functional and structural interactions between measles virus haemagglutinin and CD46. J Virol 69: 3 341–3 349Google Scholar
  45. 45.
    Ohuchi M, Ohuchi R, Mifune K, Ishihara T, Ogawa T (1987) Characterization of the measles virus isolated from the brain of a patient with immunosuppressive measles encephalitis. J Infect Dis 156: 436–441PubMedCrossRefGoogle Scholar
  46. 46.
    Patterson JB, Samuel CE (1995) Expression and regulation by interferon of a double stranded-RNA-specific adenosine desaminase from human cells: evidence for two forms of the deaminase. Mol Cell Biol 15: 5 376–5 388Google Scholar
  47. 47.
    Radecke F, Spielhofer P, Schneider H, Kaelin K, Huber M, Dötsch C, Christiansen G, Billeter MA (1995) Rescue of measles virus from cloned cDNA. EMBO J 14: 5 773–5 784Google Scholar
  48. 48.
    Rager-Zisman B, Egan JE, Kress Y, Bloom BR (1984) Isolation of cold-sensitive mutants of measles virus from persistently infected murine neuroblastoma cells. J Virol 51: 845–855PubMedGoogle Scholar
  49. 49.
    Rataul SM, Hirano A, Wong TC (1992) Irreversible modification of measles virus RNA in vitro by nuclear RNA-unwinding activity in human neuroblastoma cells. J Virol 66: 1769–1773PubMedGoogle Scholar
  50. 50.
    Rima BK, Earle JAP, Baczko K, Rota PA, Bellini WJ (1995) Measles virus strain variations. Curr Topics Microbiol Immunol 191: 65–83CrossRefGoogle Scholar
  51. 51.
    Sanchez-Lanier M, Guerlin P, Mclaren LC, Bankhurst AD (1988) Measles virus induced suppression of lymphocyte proliferation. Cell Immunol 116: 367–381PubMedCrossRefGoogle Scholar
  52. 52.
    Schlender J, Schnorr JJ, Spielhofer P, Cathomen T, Cattaneo R, Billeter MA, ter Meulen V, Schneider-Schaulies S (1996) Interaction of measles virus glycoproteins with the surface of uninfected peripheral blood lymphocytes induces immunosuppression in vitro. Proc Natl Acad Sci USK 93: 13 194–13 199Google Scholar
  53. 53.
    Schmid A, Cattaneo R, Billeter MA (1987) A procedure for selective full length cDNA cloning of specific RNA species. Nucleic Acids Res 15: 3 987–3 996CrossRefGoogle Scholar
  54. 54.
    Schmid A, Spielhofer P, Cattaneo R, Baczko K, ter Meulen V, Billeter MA (1992) Subacute sclerosing panencephalitis is typically characterized by alteration in the fusion protein cytoplasmic domain of persisting measles virus. Virology 188: 910–915PubMedCrossRefGoogle Scholar
  55. 55.
    Schneider-Schaulies J, Dunster LM, Schwartz-Albiez R, Krohne G, ter Meulen V (1995) Physical association of moesin and CD46 as a receptor complex for measles virus. J Virol 69: 2248–2256PubMedGoogle Scholar
  56. 56.
    Schneider-Schaulies J, Schnorr JJ, Brinckmann U, Dunster LM, Baczko K, Schneider-Schaulies S, ter Meulen V (1995) Receptor usage and differential downregulation of CD46 by measles virus wild type and vaccine strains. Proc Natl Acad Sci USA 92: 3 943–3 947CrossRefGoogle Scholar
  57. 57.
    Schneider-Schaulies J, Dunster LM, Kobune F, Rima BK, ter Meulen V (1995) Differential downregulation of CD46 by measles virus strains. J Virol 69: 7 257–7 259Google Scholar
  58. 58.
    Schneider-Schaulies J, Schnorr JJ, Schlender J, Dunster LM, Schneider-Schaulies S, ter Meulen V (1996) Receptor (CD46) modulation and complement mediated lysis of uninfected cells after contact with measles virus infected cells. J Virol 70: 255–263PubMedGoogle Scholar
  59. 59.
    Schneider-Schaulies S, Kreth HW, Hofmann G, Billeter M, ter Meulen V (1991) Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autommue diseases. Virology 182: 703–711PubMedCrossRefGoogle Scholar
  60. 60.
    Schneider-Schaulies S, ter Meulen V (1992) Molecular aspcts of measles virus induced central nervous system diseases. In Ross RP (ed) Molecular neurovirology. Humana Press, Clifton, pp 419–449CrossRefGoogle Scholar
  61. 61.
    Schneider-Schaulies S, Schneider-Schaulies J, Bayer M, Löffler S, ter Meulen V (1993) Spontaneous and differentiation dependent regulation of measles virus gene expression in human glial cells. J Virol 67: 3 375–3 383Google Scholar
  62. 62.
    Schneider-Schaulies S, Liebert UG, Baczko K, ter Meulen V (1990) Restricted expression of measles virus in primary rat astroglial cells. Virology 177: 802–806PubMedCrossRefGoogle Scholar
  63. 63.
    Schneider-Schaulies S, Liebert UG, Baczko K, Cattaneo R, Billeter M, ter Meulen V (1989) Restriction of measles virus gene expression in acute and subacute encephalitis of Lewis rats. Virology 171: 525–534PubMedCrossRefGoogle Scholar
  64. 64.
    Schneider-Schaulies S, Liebert UG, Segev Y, Rager-Zisman B, Wolfson M, ter Meulen V (1992) Antibody-dependent transcriptional regulation of measles virus in persistently infected neural cells. J Virol 66: 5 534–5 541Google Scholar
  65. 65.
    Schneider-Schaulies S, Schuster A, Schneider-Schaulies J, Bayer M, Pavlovic J, ter Meulen V (1994) Cell type specific MxA-mediated inhibition of measles virus transcription in human brain cells. J Virol 68: 6910–6917PubMedGoogle Scholar
  66. 66.
    Schnorr JJ, Schneider-Schaulies S, Simon-Jödicke A, Pavlovic J, Horisberger MA, ter Meulen V (1993) MxA dependent inhibition of measles virus glycoprotein synthesis in a stably transfected human monocytic cell line. J Virol 67: 4 760–4 768Google Scholar
  67. 67.
    Schnorr JJ, Dunster LM, Nanan R, Schneider-Schaulies J, Schneider-Schaulies S, ter Meulen V (1995) Measles virus induced downregulation of CD46 is associated with enhanced sensitivity to complement mediated lysis of infected cells. Eur J Immunol 25: 976–984PubMedCrossRefGoogle Scholar
  68. 68.
    Schnorr JJ, Seufert M, Schlender J, Borst J, Johnston ICD, ter Meulen V, Schneider-Schaulies S (1997) Cell cycle arrest rather than apoptosis is associated with measles virus contact-mediated immunosuppression in vitro. J Gen Virol 78: 3 217–3 226Google Scholar
  69. 69.
    Schnorr JJ, Xanthakos S, Keikavoussi P, Kämpgen E, ter Meulen V, Schneider-Schaulies S (1997) Induction of maturation of human blood dendritic cell precursors by measles virus is associated with immunosuppression. Proc Natl Acad Sci USA 94: 5 326–5331CrossRefGoogle Scholar
  70. 70.
    Spielhofer P, Bächi T, Fehr T, Christiansen G, Cattaneo R, Kaelin K, Billeter MA, Nairn HY (1998) Chimeric measles viruses with a foreign envelope. J Virol 72: 2 150–2 159Google Scholar
  71. 71.
    Schuster A, Johnston ICD, Das T, Banerjee AK, Pavlovic J, Schneider-Schaulies S (1996) MxA expression in human brain cells is associated with hyperphosphorylation of P protein of VSV. Virology 220: 241–245PubMedCrossRefGoogle Scholar
  72. 72.
    Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Ann Rev Immunol 9: 271–196CrossRefGoogle Scholar
  73. 73.
    Vanchiere JA, Bellini WJ, Moyer SA (1995) Hypermutation of the phosphoprotein and altered mRNA editing in the hamster neurotropic strain of measles. Virology 207: 555–5 561PubMedCrossRefGoogle Scholar
  74. 74.
    Watanabe M, Hirano A, Stenglein S, Nelson J, Thomas G, Wong TC (1995) Engineered serine protease inhibitor prevent furin-catalysed activation of the fusion glyprotein and production of infectious measles virus. J Virol 69: 3 206–3 210Google Scholar
  75. 75.
    Wild TF, Malvoisin E, Buckland R (1991) Measles virus: both the haemagglutinin and the fusion glycoproteins are required for fusion. J Gen Virol 72: 439–442PubMedCrossRefGoogle Scholar
  76. 76.
    Wong TC, Ayata M, Ueda S, Hirano A (1991) Role of baised hypermutation in evolution of subacute sclerosing panencephalitis virus from progenitor acute measles virus. J Virol 65: 2191–2199PubMedGoogle Scholar
  77. 77.
    Wyde PR, Ambrosi MW, Voss TG, Meyer HL, Gilbert BF (1992) Measles virus replication in lungs of hispid cotton rats after intranasal inoculation. Proc Soc Exp Biol Med 24: 80–87Google Scholar
  78. 78.
    Yanagi Y, Cubitt BA, Oldstone MBA (1992) Measles virus inhibits mitogen-induced T cell proliferation. Virology 187: 280–289PubMedCrossRefGoogle Scholar
  79. 79.
    Yoshikawa Y, Yamanouchi K (1984) Effects of papaverine treatment on replication of measles virus in human neural and non-neural cells. J Virol 50: 489–495PubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 1999

Authors and Affiliations

  • S. Schneider-Schaulies
    • 1
  • V. ter Meulen
    • 1
  1. 1.Institute of Virology and ImmunobiologyUniversity of WürzburgWürzburgGermany

Personalised recommendations