Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1992 Mar;66(3):1769–1773. doi: 10.1128/jvi.66.3.1769-1773.1992

Irreversible modification of measles virus RNA in vitro by nuclear RNA-unwinding activity in human neuroblastoma cells.

S M Rataul 1, A Hirano 1, T C Wong 1
PMCID: PMC240933  PMID: 1738207

Abstract

The matrix (M) gene of a measles virus (MV) variant passaged in IMR-32 human neuroblastoma cells displays numerous uridine-to-cytosine transitions called biased hypermutation. Using an in vitro assay, we show that IMR-32 cells contain high levels of an activity which unwinds and irreversibly alters the base pairing of double-stranded RNA synthesized from the M gene of MV. This activity is found exclusively in the cellular nucleus and is present at a lower level in African green monkey kidney Vero cells. Experiments with mixed cell extracts suggest that the low activity in Vero cells is not due to inhibitory factors. These findings support the hypothesis that this RNA-modifying and -unwinding activity is responsible for biased hypermutation of MV strains that infect the central nervous system. Possible functions of this neural cell activity and implications for central nervous system disorders are discussed.

Full text

PDF
1770

Images in this article

1770Image
on p.1770
1770Image
on p.1770
1771Image
on p.1771
1771Image
on p.1771

Selected References

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

  1. Ayata M., Hirano A., Wong T. C. Altered translation of the matrix genes in Niigata and Yamagata neurovirulent measles virus strains. Virology. 1991 Jan;180(1):166–174. doi: 10.1016/0042-6822(91)90020-c. [DOI] [PubMed] [Google Scholar]
  2. Ayata M., Hirano A., Wong T. C. Structural defect linked to nonrandom mutations in the matrix gene of biken strain subacute sclerosing panencephalitis virus defined by cDNA cloning and expression of chimeric genes. J Virol. 1989 Mar;63(3):1162–1173. doi: 10.1128/jvi.63.3.1162-1173.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baczko K., Liebert U. G., Billeter M., 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 Aug;59(2):472–478. doi: 10.1128/jvi.59.2.472-478.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bass B. L., Weintraub H. An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell. 1988 Dec 23;55(6):1089–1098. doi: 10.1016/0092-8674(88)90253-x. [DOI] [PubMed] [Google Scholar]
  5. Bass B. L., Weintraub H., Cattaneo R., Billeter M. A. Biased hypermutation of viral RNA genomes could be due to unwinding/modification of double-stranded RNA. Cell. 1989 Feb 10;56(3):331–331. doi: 10.1016/0092-8674(89)90234-1. [DOI] [PubMed] [Google Scholar]
  6. Carter C., Black F. L., Schluederberg A. Nucleus-associated RNA in measles virus-infected cells. Biochem Biophys Res Commun. 1973 Sep 5;54(1):411–416. doi: 10.1016/0006-291x(73)90937-6. [DOI] [PubMed] [Google Scholar]
  7. Cattaneo R., Schmid A., Billeter M. A., Sheppard R. D., Udem S. A. Multiple viral mutations rather than host factors cause defective measles virus gene expression in a subacute sclerosing panencephalitis cell line. J Virol. 1988 Apr;62(4):1388–1397. doi: 10.1128/jvi.62.4.1388-1397.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cattaneo R., Schmid A., Eschle D., Baczko K., ter Meulen V., Billeter M. A. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988 Oct 21;55(2):255–265. doi: 10.1016/0092-8674(88)90048-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cattaneo R., Schmid A., Spielhofer P., Kaelin K., Baczko K., ter Meulen V., Pardowitz J., Flanagan S., Rima B. K., Udem S. A. Mutated and hypermutated genes of persistent measles viruses which caused lethal human brain diseases. Virology. 1989 Dec;173(2):415–425. doi: 10.1016/0042-6822(89)90554-0. [DOI] [PubMed] [Google Scholar]
  10. Dubois-Dalcq M. Pathology of measles virus infection of the nervous system: comparison with multiple sclerosis. Int Rev Exp Pathol. 1979;19:101–135. [PubMed] [Google Scholar]
  11. Dörries R., ter Meulen V. Specificity of IgM antibodies in acute human coxsackievirus B infections, analysed by indirect solid phase enzyme immunoassay and immunoblot technique. J Gen Virol. 1983 Jan;64(Pt 1):159–167. doi: 10.1099/0022-1317-64-1-159. [DOI] [PubMed] [Google Scholar]
  12. Enami M., Sato T. A., Sugiura A. Matrix protein of cell-associated subacute sclerosing panencephalitis viruses. J Gen Virol. 1989 Aug;70(Pt 8):2191–2196. doi: 10.1099/0022-1317-70-8-2191. [DOI] [PubMed] [Google Scholar]
  13. Follett E. A., Pringle C. R., Pennington T. H. Events following the infections of enucleate cells with measles virus. J Gen Virol. 1976 Aug;32(2):163–175. doi: 10.1099/0022-1317-32-2-163. [DOI] [PubMed] [Google Scholar]
  14. Kimelman D., Kirschner M. W. An antisense mRNA directs the covalent modification of the transcript encoding fibroblast growth factor in Xenopus oocytes. Cell. 1989 Nov 17;59(4):687–696. doi: 10.1016/0092-8674(89)90015-9. [DOI] [PubMed] [Google Scholar]
  15. Kipps A., Dick G., Moodie J. W. Measles and the central nervous system. Lancet. 1983 Dec 17;2(8364):1406–1410. doi: 10.1016/s0140-6736(83)90932-7. [DOI] [PubMed] [Google Scholar]
  16. Kristensson K., Norrby E. Persistence of RNA viruses in the central nervous system. Annu Rev Microbiol. 1986;40:159–184. doi: 10.1146/annurev.mi.40.100186.001111. [DOI] [PubMed] [Google Scholar]
  17. Lamb R. A., Dreyfuss G. RNA structure. Unwinding with a vengeance. Nature. 1989 Jan 5;337(6202):19–20. doi: 10.1038/337019a0. [DOI] [PubMed] [Google Scholar]
  18. Liebert U. G., Baczko K., Budka H., ter Meulen V. Restricted expression of measles virus proteins in brains from cases of subacute sclerosing panencephalitis. J Gen Virol. 1986 Nov;67(Pt 11):2435–2444. doi: 10.1099/0022-1317-67-11-2435. [DOI] [PubMed] [Google Scholar]
  19. Manley J. L., Fire A., Samuels M., Sharp P. A. In vitro transcription: whole-cell extract. Methods Enzymol. 1983;101:568–582. doi: 10.1016/0076-6879(83)01038-1. [DOI] [PubMed] [Google Scholar]
  20. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morrissey L. M., Kirkegaard K. Regulation of a double-stranded RNA modification activity in human cells. Mol Cell Biol. 1991 Jul;11(7):3719–3725. doi: 10.1128/mcb.11.7.3719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oyanagi S., ter Meulen V., Katz M., Koprowski H. Comparison of subacute sclerosing panencephalitis and measles viruses: an electron microscope study. J Virol. 1971 Jan;7(1):176–187. doi: 10.1128/jvi.7.1.176-187.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oyanagi S., ter Meulen V., Müller D., Katz M., Koprowski H. Electron microscopic observations in subacute sclerosing panencephalitis brain cell cultures: their correlation with cytochemical and immunocytological findings. J Virol. 1970 Sep;6(3):370–379. doi: 10.1128/jvi.6.3.370-379.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raine C. S., Feldman L. A., Sheppard R. D., Bornstein M. B. Ultrastructural study of long-term measles infection in cultures of hamster dorsal-root ganglion. J Virol. 1971 Sep;8(3):318–329. doi: 10.1128/jvi.8.3.318-329.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Raine C. S., Feldman L. A., Sheppard R. D., Bornstein M. B. Ultrastructure of measles virus in cultures of hamster cerebellum. J Virol. 1969 Aug;4(2):169–181. doi: 10.1128/jvi.4.2.169-181.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schluederberg A., Chavanich S. The role of the nucleus in measles virus replication. Med Microbiol Immunol. 1974;160(2-3):85–90. doi: 10.1007/BF02121715. [DOI] [PubMed] [Google Scholar]
  27. Sommer B., Köhler M., Sprengel R., Seeburg P. H. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991 Oct 4;67(1):11–19. doi: 10.1016/0092-8674(91)90568-j. [DOI] [PubMed] [Google Scholar]
  28. Wagner R. W., Nishikura K. Cell cycle expression of RNA duplex unwindase activity in mammalian cells. Mol Cell Biol. 1988 Feb;8(2):770–777. doi: 10.1128/mcb.8.2.770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wechsler S. L., Fields B. N. Intracellular synthesis of measles virus-specified polypeptides. J Virol. 1978 Jan;25(1):285–297. doi: 10.1128/jvi.25.1.285-297.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wechsler S. L., Meissner H. C. Measles and SSPE viruses: similarities and differences. Prog Med Virol. 1982;28:65–95. [PubMed] [Google Scholar]
  31. Wong T. C., Ayata M., Hirano A., Yoshikawa Y., Tsuruoka H., Yamanouchi K. Generalized and localized biased hypermutation affecting the matrix gene of a measles virus strain that causes subacute sclerosing panencephalitis. J Virol. 1989 Dec;63(12):5464–5468. doi: 10.1128/jvi.63.12.5464-5468.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wong T. C., Ayata M., Ueda S., Hirano A. Role of biased hypermutation in evolution of subacute sclerosing panencephalitis virus from progenitor acute measles virus. J Virol. 1991 May;65(5):2191–2199. doi: 10.1128/jvi.65.5.2191-2199.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wong T. C., Wipf G., Hirano A. The measles virus matrix gene and gene product defined by in vitro and in vivo expression. Virology. 1987 Apr;157(2):497–508. doi: 10.1016/0042-6822(87)90292-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES