Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1985 Oct;56(1):201–206. doi: 10.1128/jvi.56.1.201-206.1985

Inhibition of influenza viral mRNA synthesis in cells expressing the interferon-induced Mx gene product.

R M Krug, M Shaw, B Broni, G Shapiro, O Haller
PMCID: PMC252506  PMID: 2411949

Abstract

Interferons alpha and beta induce an efficient antiviral state against influenza virus in mouse cells that possess the Mx gene, but not in mouse cells that lack this gene. In Mx-containing cells treated with interferon the amount of viral mRNA synthesized as a result of primary transcription is drastically reduced. Only two viral mRNAs could be detected by Northern analysis and by translating the poly(A)+ RNA from infected cells in wheat germ extracts: a reduced amount of the mRNA for nonstructural protein 1 and an even lower amount of the mRNA for the matrix protein. The other viral mRNAs were not made in detectable amounts. In addition, the rate of viral mRNA synthesis catalyzed by the inoculum transcriptase, measured by in vitro RNA synthesis catalyzed by permeabilized cells, was severely inhibited. In contrast, interferon treatment of cells lacking the Mx gene had little or no effect on either the steady-state level or the rate of synthesis of viral mRNAs made by the inoculum transcriptase. These results indicate that the interferon-induced Mx gene product, a 75,000-molecular-weight protein that accumulates in the nucleus, inhibits influenza viral mRNA synthesis which occurs in the nucleus. No Mx-specific effect acting directly on viral protein synthesis in the cytoplasm was observed.

Full text

PDF

Images in this article

202Image
on p.202
203Image
on p.203
203Image
on p.203
204Image
on p.204
205Image
on p.205

Selected References

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

  1. Arnheiter H., Staeheli P. Expression of interferon dependent resistance to influenza virus in mouse embryo cells. Arch Virol. 1983;76(2):127–137. doi: 10.1007/BF01311696. [DOI] [PubMed] [Google Scholar]
  2. Beaton A. R., Krug R. M. Synthesis of the templates for influenza virion RNA replication in vitro. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4682–4686. doi: 10.1073/pnas.81.15.4682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Collins P. L., Hightower L. E., Ball L. A. Transcription and translation of Newcastle disease virus mRNA's in vitro. J Virol. 1978 Oct;28(1):324–336. doi: 10.1128/jvi.28.1.324-336.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dreiding P., Staeheli P., Haller O. Interferon-induced protein Mx accumulates in nuclei of mouse cells expressing resistance to influenza viruses. Virology. 1985 Jan 15;140(1):192–196. doi: 10.1016/0042-6822(85)90460-x. [DOI] [PubMed] [Google Scholar]
  5. Haller O., Arnheiter H., Lindenmann J., Gresser I. Host gene influences sensitivity to interferon action selectively for influenza virus. Nature. 1980 Feb 14;283(5748):660–662. doi: 10.1038/283660a0. [DOI] [PubMed] [Google Scholar]
  6. Haller O. Inborn resistance of ice to orthomyxoviruses. Curr Top Microbiol Immunol. 1981;92:25–52. doi: 10.1007/978-3-642-68069-4_3. [DOI] [PubMed] [Google Scholar]
  7. Herz C., Stavnezer E., Krug R., Gurney T., Jr Influenza virus, an RNA virus, synthesizes its messenger RNA in the nucleus of infected cells. Cell. 1981 Nov;26(3 Pt 1):391–400. doi: 10.1016/0092-8674(81)90208-7. [DOI] [PubMed] [Google Scholar]
  8. Horisberger M. A., Staeheli P., Haller O. Interferon induces a unique protein in mouse cells bearing a gene for resistance to influenza virus. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1910–1914. doi: 10.1073/pnas.80.7.1910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Katze M. G., Krug R. M. Metabolism and expression of RNA polymerase II transcripts in influenza virus-infected cells. Mol Cell Biol. 1984 Oct;4(10):2198–2206. doi: 10.1128/mcb.4.10.2198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Krug R. M. Influenza viral RNPs newly synthesized during the latent period of viral growth in MDCK cells. Virology. 1971 Apr;44(1):125–136. doi: 10.1016/0042-6822(71)90159-0. [DOI] [PubMed] [Google Scholar]
  11. Krug R. M. Priming of influenza viral RNA transcription by capped heterologous RNAs. Curr Top Microbiol Immunol. 1981;93:125–149. doi: 10.1007/978-3-642-68123-3_6. [DOI] [PubMed] [Google Scholar]
  12. Lamb R. A., Choppin P. W. Synthesis of influenza virus proteins in infected cells: translation of viral polypeptides, including three P polypeptides, from RNA produced by primary transcription. Virology. 1976 Oct 15;74(2):504–519. doi: 10.1016/0042-6822(76)90356-1. [DOI] [PubMed] [Google Scholar]
  13. Lamb R. A., Etkind P. R., Choppin P. W. Evidence for a ninth influenza viral polypeptide. Virology. 1978 Nov;91(1):60–78. doi: 10.1016/0042-6822(78)90355-0. [DOI] [PubMed] [Google Scholar]
  14. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  15. Mason W. S., Aldrich C., Summers J., Taylor J. M. Asymmetric replication of duck hepatitis B virus DNA in liver cells: Free minus-strand DNA. Proc Natl Acad Sci U S A. 1982 Jul;79(13):3997–4001. doi: 10.1073/pnas.79.13.3997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Meyer T., Horisberger M. A. Combined action of mouse alpha and beta interferons in influenza virus-infected macrophages carrying the resistance gene Mx. J Virol. 1984 Mar;49(3):709–716. doi: 10.1128/jvi.49.3.709-716.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miller M. R., Castellot J. J., Jr, Pardee A. B. A permeable animal cell preparation for studying macromolecular synthesis. DNA synthesis and the role of deoxyribonucleotides in S phase initiation. Biochemistry. 1978 Mar 21;17(6):1073–1080. doi: 10.1021/bi00599a021. [DOI] [PubMed] [Google Scholar]
  18. Peluso R. W., Lamb R. A., Choppin P. W. Polypeptide synthesis in simian virus 5-infected cells. J Virol. 1977 Jul;23(1):177–187. doi: 10.1128/jvi.23.1.177-187.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Plotch S. J., Krug R. M. Segments of influenza virus complementary RNA synthesized in vitro. J Virol. 1978 Feb;25(2):579–586. doi: 10.1128/jvi.25.2.579-586.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Staeheli P., Horisberger M. A., Haller O. Mx-dependent resistance to influenza viruses is induced by mouse interferons alpha and beta but not gamma. Virology. 1984 Jan 30;132(2):456–461. doi: 10.1016/0042-6822(84)90050-3. [DOI] [PubMed] [Google Scholar]
  21. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES