Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1994 Nov;68(11):6910–6917. doi: 10.1128/jvi.68.11.6910-6917.1994

Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells.

S Schneider-Schaulies 1, J Schneider-Schaulies 1, A Schuster 1, M Bayer 1, J Pavlovic 1, V ter Meulen 1
PMCID: PMC237126  PMID: 7933071

Abstract

Measles virus (MV)-specific transcription in human brain cells is characterized by particularly low abundances of the distal mRNAs encoding the MV envelope proteins. Similar transcriptional restrictions of the closely related vesicular stomatitis virus have been observed in mouse fibroblasts constitutively expressing the interferon-inducible MxA protein (P. Staeheli and J. Pavlovic, J. Virol. 65:4498-4501, 1991). We found that MV infection of human brain cells is accompanied by rapid induction and high-level expression of endogenous MxA proteins. After stable transfection of MxA, human glioblastoma cells (U-87-MxA) released 50- to 100-fold less infectious virus and expression of viral proteins was highly restricted. The overall MV-specific transcription levels were reduced by up to 90%, accompanied by low relative frequencies of the distal MV-specific mRNAs. These restrictions were linked to an inhibition of viral RNA synthesis and not to a decreased stability of the viral RNAs. Our results indicate that expression of MxA is associated with transcriptional attenuation of MV in brain cells, thus probably contributing to the establishment of persistent MV central nervous system infections. In addition, the mechanism of MxA-dependent resistance against MV infection, in contrast to that of vesicular stomatitis virus, is cell type specific, because an inhibition of MV glycoprotein synthesis independent of transcriptional alterations was observed in MxA-transfected human monocytes (J. J. Schnorr, S. Schneider-Schaulies, A. Simon-Jödicke, J. Pavlovic, M. A. Horisberger, and V. ter Meulen, J. Virol. 67: 4760-4768, 1993).

Full text

PDF
6910

Images in this article

6912Image
on p.6912
6913Image
on p.6913
6914Image
on p.6914
6914Image
on p.6914
6915Image
on p.6915

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aebi M., Fäh J., Hurt N., Samuel C. E., Thomis D., Bazzigher L., Pavlovic J., Haller O., Staeheli P. cDNA structures and regulation of two interferon-induced human Mx proteins. Mol Cell Biol. 1989 Nov;9(11):5062–5072. doi: 10.1128/mcb.9.11.5062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bigner D. D., Bigner S. H., Pontén J., Westermark B., Mahaley M. S., Ruoslahti E., Herschman H., Eng L. F., Wikstrand C. J. Heterogeneity of Genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol. 1981 May;40(3):201–229. doi: 10.1097/00005072-198105000-00001. [DOI] [PubMed] [Google Scholar]
  3. Billeter M. A., Cattaneo R., Spielhofer P., Kaelin K., Huber M., Schmid A., Baczko K., ter Meulen V. Generation and properties of measles virus mutations typically associated with subacute sclerosing panencephalitis. Ann N Y Acad Sci. 1994 Jun 6;724:367–377. doi: 10.1111/j.1749-6632.1994.tb38934.x. [DOI] [PubMed] [Google Scholar]
  4. Carrigan D. R., Knox K. K. Identification of interferon-resistant subpopulations in several strains of measles virus: positive selection by growth of the virus in brain tissue. J Virol. 1990 Apr;64(4):1606–1615. doi: 10.1128/jvi.64.4.1606-1615.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cattaneo R., Rebmann G., Baczko K., ter Meulen V., Billeter M. A. Altered ratios of measles virus transcripts in diseased human brains. Virology. 1987 Oct;160(2):523–526. doi: 10.1016/0042-6822(87)90031-6. [DOI] [PubMed] [Google Scholar]
  6. Cattaneo R., Rebmann G., Schmid A., Baczko K., ter Meulen V., Billeter M. A. Altered transcription of a defective measles virus genome derived from a diseased human brain. EMBO J. 1987 Mar;6(3):681–688. doi: 10.1002/j.1460-2075.1987.tb04808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gunning P., Leavitt J., Muscat G., Ng S. Y., Kedes L. A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4831–4835. doi: 10.1073/pnas.84.14.4831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hall W. W., Genius D., ter Meulen V. The effect of cycloheximide on the replication of measles virus. J Gen Virol. 1977 Jun;35(3):579–582. doi: 10.1099/0022-1317-35-3-579. [DOI] [PubMed] [Google Scholar]
  10. Horisberger M. A. Interferon-induced human protein MxA is a GTPase which binds transiently to cellular proteins. J Virol. 1992 Aug;66(8):4705–4709. doi: 10.1128/jvi.66.8.4705-4709.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Horisberger M. A., McMaster G. K., Zeller H., Wathelet M. G., Dellis J., Content J. Cloning and sequence analyses of cDNAs for interferon- and virus-induced human Mx proteins reveal that they contain putative guanine nucleotide-binding sites: functional study of the corresponding gene promoter. J Virol. 1990 Mar;64(3):1171–1181. doi: 10.1128/jvi.64.3.1171-1181.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Huang T., Pavlovic J., Staeheli P., Krystal M. Overexpression of the influenza virus polymerase can titrate out inhibition by the murine Mx1 protein. J Virol. 1992 Jul;66(7):4154–4160. doi: 10.1128/jvi.66.7.4154-4160.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huttenlocher P. R., Picchietti D. L., Roos R. P., Cashman N. R., Horowitz B., Horowitz M. S. Intrathecal interferon in subacute sclerosing panencephalitis. Ann Neurol. 1986 Mar;19(3):303–305. doi: 10.1002/ana.410190317. [DOI] [PubMed] [Google Scholar]
  14. Joncas J. H., Robillard L. R., Boudreault A., Leyritz M., McLaughlin B. J. Letter: Interferon in serum and cerebrospinal fluid in subacute sclerosing panencephalitis. Can Med Assoc J. 1976 Aug 21;115(4):309–309. [PMC free article] [PubMed] [Google Scholar]
  15. Kraus E., Schneider-Schaulies S., Miyasaka M., Tamatani T., Sedgwick J. Augmentation of major histocompatibility complex class I and ICAM-1 expression on glial cells following measles virus infection: evidence for the role of type-1 interferon. Eur J Immunol. 1992 Jan;22(1):175–182. doi: 10.1002/eji.1830220126. [DOI] [PubMed] [Google Scholar]
  16. Krug R. M., Shaw M., Broni B., Shapiro G., Haller O. Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product. J Virol. 1985 Oct;56(1):201–206. doi: 10.1128/jvi.56.1.201-206.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kumar R., Chattopadhyay D., Banerjee A. K., Sen G. C. Ribonuclease activity is associated with subviral particles isolated from interferon-treated vesicular stomatitis virus-infected cells. J Virol. 1988 Feb;62(2):641–643. doi: 10.1128/jvi.62.2.641-643.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miyazu M., Morishima T., Hanada N., Isomura S., Suzuki S. Types of interferons detected in cerebrospinal fluid from patients with viral infections of the central nervous system. J Infect Dis. 1985 Nov;152(5):1098–1099. doi: 10.1093/infdis/152.5.1098a. [DOI] [PubMed] [Google Scholar]
  19. Moyer S. A., Baker S. C., Horikami S. M. Host cell proteins required for measles virus reproduction. J Gen Virol. 1990 Apr;71(Pt 4):775–783. doi: 10.1099/0022-1317-71-4-775. [DOI] [PubMed] [Google Scholar]
  20. Moyer S. A., Baker S. C., Lessard J. L. Tubulin: a factor necessary for the synthesis of both Sendai virus and vesicular stomatitis virus RNAs. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5405–5409. doi: 10.1073/pnas.83.15.5405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ogura H., Baczko K., Rima B. K., ter Meulen V. Selective inhibition of translation of the mRNA coding for measles virus membrane protein at elevated temperatures. J Virol. 1987 Feb;61(2):472–479. doi: 10.1128/jvi.61.2.472-479.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pavlovic J., Haller O., Staeheli P. Human and mouse Mx proteins inhibit different steps of the influenza virus multiplication cycle. J Virol. 1992 Apr;66(4):2564–2569. doi: 10.1128/jvi.66.4.2564-2569.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pavlovic J., Zürcher T., Haller O., Staeheli P. Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein. J Virol. 1990 Jul;64(7):3370–3375. doi: 10.1128/jvi.64.7.3370-3375.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pitossi F., Blank A., Schröder A., Schwarz A., Hüssi P., Schwemmle M., Pavlovic J., Staeheli P. A functional GTP-binding motif is necessary for antiviral activity of Mx proteins. J Virol. 1993 Nov;67(11):6726–6732. doi: 10.1128/jvi.67.11.6726-6732.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rager-Zisman B., Egan J. E., Kress Y., Bloom B. R. Isolation of cold-sensitive mutants of measles virus from persistently infected murine neuroblastoma cells. J Virol. 1984 Sep;51(3):845–855. doi: 10.1128/jvi.51.3.845-855.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ronni T., Melén K., Malygin A., Julkunen I. Control of IFN-inducible MxA gene expression in human cells. J Immunol. 1993 Mar 1;150(5):1715–1726. [PubMed] [Google Scholar]
  27. Schneider-Schaulies J., Schneider-Schaulies S., Ter Meulen V. Differential induction of cytokines by primary and persistent measles virus infections in human glial cells. Virology. 1993 Jul;195(1):219–228. doi: 10.1006/viro.1993.1363. [DOI] [PubMed] [Google Scholar]
  28. Schneider-Schaulies S., Liebert U. G., Baczko K., ter Meulen V. Restricted expression of measles virus in primary rat astroglial cells. Virology. 1990 Aug;177(2):802–806. doi: 10.1016/0042-6822(90)90553-4. [DOI] [PubMed] [Google Scholar]
  29. Schneider-Schaulies S., Liebert U. G., Segev Y., Rager-Zisman B., Wolfson M., ter Meulen V. Antibody-dependent transcriptional regulation of measles virus in persistently infected neural cells. J Virol. 1992 Sep;66(9):5534–5541. doi: 10.1128/jvi.66.9.5534-5541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schneider-Schaulies S., Schneider-Schaulies J., Bayer M., Löffler S., ter Meulen V. Spontaneous and differentiation-dependent regulation of measles virus gene expression in human glial cells. J Virol. 1993 Jun;67(6):3375–3383. doi: 10.1128/jvi.67.6.3375-3383.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schnorr J. J., Schneider-Schaulies S., Simon-Jödicke A., Pavlovic J., Horisberger M. A., ter Meulen V. MxA-dependent inhibition of measles virus glycoprotein synthesis in a stably transfected human monocytic cell line. J Virol. 1993 Aug;67(8):4760–4768. doi: 10.1128/jvi.67.8.4760-4768.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Staeheli P. Interferon-induced proteins and the antiviral state. Adv Virus Res. 1990;38:147–200. doi: 10.1016/s0065-3527(08)60862-3. [DOI] [PubMed] [Google Scholar]
  33. Staeheli P., Pavlovic J. Inhibition of vesicular stomatitis virus mRNA synthesis by human MxA protein. J Virol. 1991 Aug;65(8):4498–4501. doi: 10.1128/jvi.65.8.4498-4501.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Staeheli P., Pitossi F., Pavlovic J. Mx proteins: GTPases with antiviral activity. Trends Cell Biol. 1993 Aug;3(8):268–272. doi: 10.1016/0962-8924(93)90055-6. [DOI] [PubMed] [Google Scholar]
  35. Stranden A. M., Staeheli P., Pavlovic J. Function of the mouse Mx1 protein is inhibited by overexpression of the PB2 protein of influenza virus. Virology. 1993 Dec;197(2):642–651. doi: 10.1006/viro.1993.1639. [DOI] [PubMed] [Google Scholar]
  36. Wikstrand C. J., Grahmann F. C., McComb R. D., Bigner D. D. Antigenic heterogeneity of human anaplastic gliomas and glioma-derived cell lines defined by monoclonal antibodies. J Neuropathol Exp Neurol. 1985 May;44(3):229–241. doi: 10.1097/00005072-198505000-00002. [DOI] [PubMed] [Google Scholar]
  37. Yoshikawa Y., Mizumoto K., Yamanouchi K. Characterization of messenger RNAs of measles virus. J Gen Virol. 1986 Dec;67(Pt 12):2807–2812. doi: 10.1099/0022-1317-67-12-2807. [DOI] [PubMed] [Google Scholar]
  38. Yoshikawa Y., Yamanouchi K. Effect of papaverine treatment on replication of measles virus in human neural and nonneural cells. J Virol. 1984 May;50(2):489–496. doi: 10.1128/jvi.50.2.489-496.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zürcher T., Pavlovic J., Staeheli P. Mechanism of human MxA protein action: variants with changed antiviral properties. EMBO J. 1992 Apr;11(4):1657–1661. doi: 10.1002/j.1460-2075.1992.tb05212.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zürcher T., Pavlovic J., Staeheli P. Nuclear localization of mouse Mx1 protein is necessary for inhibition of influenza virus. J Virol. 1992 Aug;66(8):5059–5066. doi: 10.1128/jvi.66.8.5059-5066.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES