Abstract
One of the hallmarks of the human CNS disease subacute sclerosing panencephalitis (SSPE) is a high level of measles virus (MV) infection of oligodendrocytes. It is therefore surprising that there is only one previous report of MV infection of rat oligodendrocytes in culture and no reports of human oligodendrocyte infection in culture. In an attempt to develop a model system to study MV infection of oligodendrocytes, time-lapse confocal microscopy, immunocytochemistry, and electron microscopy (EM) were used to study infection of the human oligodendroglioma cell line, MO3.13. A rat oligodendrocyte cell line, OLN-93, was also studied as a control. MO3.13 cells were shown to be highly susceptible to MV infection and virus budding was observed from the surface of infected MO3.13 cells by EM. Analysis of the infection in real time and by immunocytochemistry revealed that virus spread occurred by cell-to-cell fusion and was also facilitated by virus transport in cell processes. MO3.13 cells were shown to express CD46, a MV receptor, but were negative for the recently discovered MV receptor, signaling leucocyte activation molecule (SLAM). Immunohistochemical studies on SSPE tissue sections demonstrated that CD46 was also expressed on populations of human oligodendrocytes. SLAM expression was not detected on oligodendrocytes. These studies, which are the first to show MV infection of human oligodendrocytes in culture, show that the cells are highly susceptible to MV infection and this model cell line has been used to further our understanding of MV spread in the CNS.
Keywords: measles virus, oligodendrocytes, neuropathogenesis, subacute sclerosing panencephalitis
References
- Agamanolis DP, Tan JS, Parker DL. Immunosuppressive measles encephalitis in a patient with a renal transplant. Arch Neurol. 1979;36:686–690. doi: 10.1001/archneur.1979.00500470056011. [DOI] [PubMed] [Google Scholar]
- Allen IV, McQuaid S, McMahon J, Kirk J, McConnell R. The significance of measles virus antigen and genome distribution in the CNS in SSPE for mechanisms of viral spread and demyelination. J Neuropathol Exp Neurol. 1996;55:471–480. doi: 10.1097/00005072-199604000-00010. [DOI] [PubMed] [Google Scholar]
- Arbour N, Cote G, Lachance C, Tardieu M, Cashman NR, Talbot PJ. Acute and persistent infection of human neural cell lines by human coronavirus OC43. J Virol. 1999;73:3350–3358. doi: 10.1128/jvi.73.4.3338-3350.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Arbour N, Ekande S, Cote G, Lachance C, Chagnon F, Tardieu M, Cashman NR, Talbot PJ. Persistent infection of human oligodendrocytic and neuroglial cell lines by human coronavirus 229E. J Virol. 1999;73:3326–3337. doi: 10.1128/jvi.73.4.3326-3337.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Askamit AR. Progressive multifocal leucoencephalopathy: a review of the pathology and pathogenesis. Microsc Res Tech. 1995;32:302–311. doi: 10.1002/jemt.1070320405. [DOI] [PubMed] [Google Scholar]
- Atkins GJ, Mooney DA, Fahy DA, Ng SH, Sheahan BJ. Multiplication of rubella and measles viruses in primary rat neural cell cultures: relevance to a postulated triggering mechanism for multiple sclerosis. Neuropathol Appl Neurobiol. 1991;17:299–308. doi: 10.1111/j.1365-2990.1991.tb00727.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baczko K, Liebert UG, Billeter MA, Cattaneo R, Budka H, ter Meulen V. Expression of defective measles virus genes in brain tissues of patients with subacute sclerosing panencephalitis. J Virol. 1986;59:472–478. doi: 10.1128/jvi.59.2.472-478.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berry M, Bannister LH, Standring SM. Nervous system. In: Berry MM, Standring SM, Bannister LH, editors. Grays Anatomy: The Anatomical Basis of Medicine and Surgery. 38 ed. London: Churchill Livingstone; 1995. pp. 901–1397. [Google Scholar]
- Billeter MA, Cattaneo R. Molecular biology of defective measles viruses persisting in the human central nervous system. In: Kingsbury D, editor. The Paramyxoviruses. New York: Plenum Press; 1991. pp. 323–345. [Google Scholar]
- Budka H, Lassmann H, Popow-Kraupp T. Measles virus antigen in panencephalitis. An immunomorphological study stressing dendritic involvement in SSPE. Acta Neuropathol (Berl) 1982;56:52–62. doi: 10.1007/BF00691182. [DOI] [PubMed] [Google Scholar]
- Cattaneo R, Schmid A, Eschle D, Baczko K, ter Meulen V, Billeter MA. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988;55:255–265. doi: 10.1016/0092-8674(88)90048-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cocks BG, Chang CC, Carballido JM, Yssel H, de Vries JE, Aversa G. A novel receptor involved in T-cell activation. Nature. 1995;376:260–263. doi: 10.1038/376260a0. [DOI] [PubMed] [Google Scholar]
- Dunster LM, Schneider-Schaulies J, Dehoff MH, Holers VM, Schwartz-Albiez R, ter Meulen V. 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. 1995;76:2085–2089. doi: 10.1099/0022-1317-76-8-2085. [DOI] [PubMed] [Google Scholar]
- Duprex WP, McQuaid S, Hangartner L, Billeter MA, Rima BK. Observation of measles virus cell-to-cell spread in astrocytoma cells by using a green fluorescent protein-expressing recombinant virus. J Virol. 1999;73:9568–9575. doi: 10.1128/jvi.73.11.9568-9575.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duprex WP, McQuaid S, Roscic-Mrkic M, Cattaneo R, McCallister C, Rima BK. In vitro and in vivo infection of neural cells by a recombinant measles virus expressing enhanced green fluorescent protein. J Virol. 2000;74:7972–7979. doi: 10.1128/JVI.74.17.7972-7979.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duprex WP, Rima BK. Green-fluorescent protein. Measles virus cell to cell spread; real-time visualisations. In: Hicks BW, editor. Methods in Molecular Biology. New York: Humana Press; 2001. [Google Scholar]
- Eggers C, Stellbrink H, Buhk T, Dorries K. Quantification of JC virus DNA in CSF of patients with HIV associated PML: a longitudinal study. J Infect Dis. 1999;180:1690–1694. doi: 10.1086/315087. [DOI] [PubMed] [Google Scholar]
- Fleury H, Bonnez W, Pometan JP, du Pasquier P. Differences in early ultrastructural aspects of the replication of measles and subacute sclerosing panencephalitis viruses in a cell culture from a human astrocytoma. J Neuropathol Exp Neurol. 1980;39:131–137. doi: 10.1097/00005072-198003000-00002. [DOI] [PubMed] [Google Scholar]
- Gates M, Sheahan BJ, O’Sullivan M, Atkins G. The pathogenicity of the A7, M9 and L10 strains of Semliki Forest virus for weanling mice and primary mouse brain cell cultures. J Gen Virol. 1985;66:2365–2373. doi: 10.1099/0022-1317-66-11-2365. [DOI] [PubMed] [Google Scholar]
- Gonzalez-Dunia D, Sauder C, de la Torre JC. Borna disease virus and the brain. Brain Res Bull. 1997;44:647–664. doi: 10.1016/S0361-9230(97)00276-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horvat B, Rivailler P, Varior-Krishnan G, Cardoso A, Gerlier D, Rarourdin-Combe C. Transgenic mice expressing human measles virus (MV) receptor CD46 provide cells exhibiting different permissivities to MV infections. J Virol. 1996;70:6673–6681. doi: 10.1128/jvi.70.10.6673-6681.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knobler RL, Stempak JG, Laurencin M. Oligodendroglial ensheathment of axons during myelination in the developing rat central nervous system. A serial section electron microscopical study. Ultrastructural Res. 1974;49:34–49. doi: 10.1016/S0022-5320(74)90076-8. [DOI] [PubMed] [Google Scholar]
- Lawrence DM, Patterson CE, Gales TL, D’Orazio JL, Vaughn MM, Rall GF. Measles virus spread between neurons requires cell contact but not CD46 expression, syncytium formation, or extracellular virus production. J Virol. 2000;74:1908–1918. doi: 10.1128/JVI.74.4.1908-1918.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liebert UG. Measles virus infections of the central nervous system. Intervirology. 1997;40:176–184. doi: 10.1159/000150544. [DOI] [PubMed] [Google Scholar]
- Ludwin SK. The perineuronal satellite oligodendrocyte. A role in remyelination. Acta Neuropathol (Berlin) 1979;47:49–53. doi: 10.1007/BF00698272. [DOI] [PubMed] [Google Scholar]
- Macintyre E, Armstrong J. Fine structural changes in human astrocyte carrier lines for measles virus. Nature. 1976;263:232–234. doi: 10.1038/263232a0. [DOI] [PubMed] [Google Scholar]
- McCarthy K, DeVellis J. Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue. J Cell Biol. 1980;85:890–902. doi: 10.1083/jcb.85.3.890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCormack D, Wallace I, Kirk J, Dinsmore S, Allen I. The establishment and characterisation of a cell line and mouse xenografts from a human malignant melanoma. Br J Exp Pathol. 1983;64:103–115. [PMC free article] [PubMed] [Google Scholar]
- McLaurin J, Trudel GC, Shaw IT, Antel JP, Cashman NR. A human glial hybrid cell line differentially expressing genes subserving oligodendrocyte and astrocyte phenotype. J Neurobiol. 1995;26:283–293. doi: 10.1002/neu.480260212. [DOI] [PubMed] [Google Scholar]
- McQuaid S, Campbell S, Wallace IJ, Kirk J, Cosby SL. Measles virus infection and replication in undifferentiated and differentiated human neuronal cells in culture. J Virol. 1998;72:5245–5250. doi: 10.1128/jvi.72.6.5245-5250.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller CA, Carrigan DR. Reversible repression and activation of measles virus infection in neural cells. Proc Natl Acad Sci USA. 1982;79:1629–1633. doi: 10.1073/pnas.79.5.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mrkic B, Pavlovic J, Rulicke T, Volpe P, Buchholz CJ, Hourcade D, Atkinson JP, Aguzzi A, Cattaneo R. Measles virus spread and pathogenesis in genetically modified mice. J Virol. 1998;72:7420–7427. doi: 10.1128/jvi.72.9.7420-7427.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mugnaini E. Membrane specializations in neuroglial cells and at neuron-glia contacts. In: Sears TA, editor. Neuronal-glial cell Interrelationships. Berlin: Springer-Verlag; 1982. pp. 39–56. [Google Scholar]
- Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, Gerlier D. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993;67:6025–6032. doi: 10.1128/jvi.67.10.6025-6032.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oldstone MB, Lewicki H, Thomas D, Tishon A, Dales S, Patterson J, Manchester M, Homann D, Naniche D, Holz A. Measles virus infection in a transgenic model: virus-induced immunosuppression and central nervous system disease. Cell. 1999;98:629–640. doi: 10.1016/S0092-8674(00)80050-1. [DOI] [PubMed] [Google Scholar]
- Reed LJ, Muench H. A simple method for estimating fifty percent endpoints. Am J Hyg. 1938;27:493–497. [Google Scholar]
- Richter-Landsberg C, Heinrich MJ. OLN-93: a new permanent oligodendroglia cell line derived from primary rat brain glial cultures. Neurosci Res. 1996;45:161–173. doi: 10.1002/(SICI)1097-4547(19960715)45:2<161::AID-JNR8>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
- Rima BK, Earle JA, Yeo RP, Herlihy L, Baczko K, ter Meulen V, Carabana J, Caballero M, Celma ML, Fernandez-Munoz R. Temporal and geographical distribution of measles virus genotypes. J Gen Virol. 1995;76:1173–1180. doi: 10.1099/0022-1317-76-5-1173. [DOI] [PubMed] [Google Scholar]
- Schneider-Schaulies S, Liebert UG, Baczko K, Cattaneo R, Billeter MA, ter Meulen V. Restriction of measles virus gene expression in acute and subacute encephalitis of Lewis rats. Virology. 1989;171:525–534. doi: 10.1016/0042-6822(89)90622-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider-Schaulies S, Liebert UG, Baczko K, ter Meulen V. Restricted expression of measles virus in primary rat astroglial cells. Virology. 1990;177:802–806. doi: 10.1016/0042-6822(90)90553-4. [DOI] [PubMed] [Google Scholar]
- Schneider-Schaulies S, Schneider-Schaulies J, Bayer M, Loffler S, ter Meulen V. Spontaneous and differentiation-dependent regulation of measles virus gene expression in human glial cells. J Virol. 1993;67:3375–3383. doi: 10.1128/jvi.67.6.3375-3383.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sidorenko SP, Clark EA. Characterization of a cell surface glycoprotein IPO-3, expressed on activated human B and T lymphocytes. J Immunol. 1993;151:4614–4624. [PubMed] [Google Scholar]
- Strelau J, Unsicker K. Expression and function in two oligodendroglial cell lines representing distinct stages of oligodendroglial development. Glia. 1999;26:291–301. doi: 10.1002/(SICI)1098-1136(199906)26:4<291::AID-GLIA3>3.0.CO;2-P. [DOI] [PubMed] [Google Scholar]
- Talbot PJ, Ekande S, Cashman NR, Mounir S, Stewart JN. Neurotropism of human coronavirus 229E. Adv Exp Med Biol. 1993;342:339–346. doi: 10.1007/978-1-4615-2996-5_52. [DOI] [PubMed] [Google Scholar]
- Tatsuo H, Ono N, Tanaka K, Yanagi Y. SLAM (CDw150) is a cellular receptor for measles virus. Nature. 2000;406:893–897. doi: 10.1038/35022579. [DOI] [PubMed] [Google Scholar]
- ter Meulen V. Molecular and cellular aspects of measles virus persistence in the CNS. J Neurovirol. 1997;3:S3–S5. [PubMed] [Google Scholar]
- ter Meulen V, Stephenson JR, Kreth HW. Subacute sclerosing panencephalitis. In: Fraenkel-Conrat H, Wagner RR, editors. Comprehensive Virology. New York: Plenum; 1983. pp. 105–109. [Google Scholar]
- Ursell MR, McLaurin J, Wood DD, Ackerley CA, Moscarello MA. Localization and partial characterization of a 60 kDa citrulline-containing transport form of myelin basic protein from MO3.13 cells and human and white matter. J Neurosci Res. 1995;42:41–53. doi: 10.1002/jnr.490420106. [DOI] [PubMed] [Google Scholar]
- Yanagi Y, Hu H, Seya T, Yoshikura H. Measles virus infects mouse fibroblast cell lines, but its multiplication is severely restricted in the absence of CD46. Arch Virol. 1994;138:39–53. doi: 10.1007/BF01310037. [DOI] [PubMed] [Google Scholar]