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. 1983 Oct;48(1):120–126. doi: 10.1128/jvi.48.1.120-126.1983

Inhibition of retrovirus DNA supercoiling in interferon-treated cells.

M Huleihel, M Aboud
PMCID: PMC255328  PMID: 6193285

Abstract

The effect of interferon (IFN) on the cytoplasmic synthesis of murine sarcoma virus DNA, its transport to the host nucleus, and its integration into the cellular genome were investigated. For this purpose, at various intervals after infection. DNA was extracted from the cytoplasmic fraction, nuclear Hirt supernatant, and chromosomal DNA pellet. The relative amount of viral DNA was estimated by C0t kinetics analysis of hybridization to murine sarcoma virus-specific [3H]cDNA. IFN was found to delay viral DNA synthesis by about 2.5 h, but the amount of viral DNA eventually formed in IFN-treated cells was comparable to that of the control. The transport of this DNA to the nucleus was delayed by IFN for 6 to 18 h, but once again, all the cytoplasmic viral DNA formed in IFN-treated cells was eventually transferred to their nucleus. However, although the main part of the viral DNA formed in control cells was finally integrated into the host genome, no significant integration was observed in IFN-treated cells. Alkaline sucrose gradient analysis revealed that IFN inhibited the accumulation of supercoiled viral DNA in the nucleus. Since supercoiled viral DNA is considered a precursor to integrated provirus, this observation may suggest that IFN inhibits viral DNA integration by blocking its supercoiling.

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Selected References

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

  1. Aboud M., Moldovan-Levin D., Salzberg S. Cytoplasmic viral DNA synthesis in exogenous infection of murine leukemia virus: effect of interferon and cycloheximide. J Virol. 1981 Feb;37(2):836–839. doi: 10.1128/jvi.37.2.836-839.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aboud M., Shoor R., Salzberg S. Adsorption, penetration, and uncoating of murine leukemia virus studied by using its reverse transcriptase. J Virol. 1979 Apr;30(1):32–37. doi: 10.1128/jvi.30.1.32-37.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aboud M., Shoor R., Salzberg S. An effect of interferon on the uncoating of murine leukaemia virus not related to the antiviral state. J Gen Virol. 1980 Dec;51(Pt 2):425–429. doi: 10.1099/0022-1317-51-2-425. [DOI] [PubMed] [Google Scholar]
  4. Aboud M., Shoor R., Salzberg S. Effect of interferon on exogenous murine leukemia virus infection. Virology. 1978 Jan;84(1):134–141. doi: 10.1016/0042-6822(78)90225-8. [DOI] [PubMed] [Google Scholar]
  5. Avery R. J., Norton J. D., Jones J. S., Burke D. C., Morris A. G. Interferon inhibits transformation by murine sarcoma viruses before integration of provirus. Nature. 1980 Nov 6;288(5786):93–95. doi: 10.1038/288093a0. [DOI] [PubMed] [Google Scholar]
  6. Ball J., McCarter J. A., Sunderland S. M. Evidence for helper independent murine sarcoma virus. I. Segregation of replication-defective and transformation-defective viruses. Virology. 1973 Nov;56(1):268–284. doi: 10.1016/0042-6822(73)90305-x. [DOI] [PubMed] [Google Scholar]
  7. Billiau A. Effect of interferon on RNA tumor viruses. Tex Rep Biol Med. 1977;35:406–419. [PubMed] [Google Scholar]
  8. Bishop J. M. Retroviruses. Annu Rev Biochem. 1978;47:35–88. doi: 10.1146/annurev.bi.47.070178.000343. [DOI] [PubMed] [Google Scholar]
  9. Chany C. Membrane-bound interferon specific cell receptor system: role in the establishment and amplification of the antiviral state. Biomedicine. 1976 Jun;24(3):148–157. [PubMed] [Google Scholar]
  10. Dales S., Hanafusa H. Penetration and intracellular release of the genomes of avian RNA tumor viruses. Virology. 1972 Nov;50(2):440–458. doi: 10.1016/0042-6822(72)90396-0. [DOI] [PubMed] [Google Scholar]
  11. Friedman R. M. Antiviral activity of interferons. Bacteriol Rev. 1977 Sep;41(3):543–567. doi: 10.1128/br.41.3.543-567.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Guntaka R. V., Mahy B. W., Bishop J. M., Varmus H. E. Ethidium bromide inhibits appearance of closed circular viral DNA and integration of virus-specific DNA in duck cells infected by avian sarcoma virus. Nature. 1975 Feb 13;253(5492):507–511. doi: 10.1038/253507a0. [DOI] [PubMed] [Google Scholar]
  13. Guntaka R. V., Richards O. C., Shank P. R., Kung H. J., Davidson N. Covalently closed circular DNA of avian sarcoma virus: purification from nuclei of infected quail tumor cells and measurement by electron microscopy and gel electrophoresis. J Mol Biol. 1976 Sep 15;106(2):337–357. doi: 10.1016/0022-2836(76)90090-5. [DOI] [PubMed] [Google Scholar]
  14. Harel J., Rassart E., Jolicoeur P. Cell cycle dependence of synthesis of unintegrated viral DNA in mouse cells newly infected with murine leukemia virus. Virology. 1981 Apr 15;110(1):202–207. doi: 10.1016/0042-6822(81)90022-2. [DOI] [PubMed] [Google Scholar]
  15. Hirt B. Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol. 1967 Jun 14;26(2):365–369. doi: 10.1016/0022-2836(67)90307-5. [DOI] [PubMed] [Google Scholar]
  16. Huleihel M., Aboud M. Effect of mouse interferon on cell transformation and virus production in rat cells exogenously infected with moloney murine sarcoma and leukemia viruses. Int J Cancer. 1982 Apr 15;29(4):471–476. doi: 10.1002/ijc.2910290418. [DOI] [PubMed] [Google Scholar]
  17. Huleihel M., Aboud M. Effect of mouse interferon on retrovirus production by chronically infected rat cells. Antiviral Res. 1982 Aug;2(3):167–175. doi: 10.1016/0166-3542(82)90019-5. [DOI] [PubMed] [Google Scholar]
  18. Jolicoeur P., Rassart E. Effect of Fv-1 gene product on synthesis of linear and supercoiled viral DNA in cells infected with murine leukemia virus. J Virol. 1980 Jan;33(1):183–195. doi: 10.1128/jvi.33.1.183-195.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jolicoeur P., Rassart E. Fate of unintegrated viral DNA in Fv-1 permissive and resistant mouse cells infected with murine leukemia virus. J Virol. 1981 Feb;37(2):609–619. doi: 10.1128/jvi.37.2.609-619.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miyamoto K., Gilden R. V. Electron microscopic studies of tumor viruses. I. Entry of murine leukemia virus into mouse embryo fibroblasts. J Virol. 1971 Mar;7(3):395–406. doi: 10.1128/jvi.7.3.395-406.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morris A. G., Burke D. C. An interferon-sensitive early step in the establishment of infection of murine cells by murine sarcoma/leukaemia virus. J Gen Virol. 1979 Apr;43(1):173–181. doi: 10.1099/0022-1317-43-1-173. [DOI] [PubMed] [Google Scholar]
  22. Morris A. G., Clegg C. The effect of mouse interferon on the transformation of NIH/3T3 mouse cells by murine sarcoma virus. Virology. 1978 Jul 15;88(2):400–402. doi: 10.1016/0042-6822(78)90298-2. [DOI] [PubMed] [Google Scholar]
  23. Riggin C. H., Pitha P. M. Effect of interferon on the exogenous Friend murine leukemia virus infection. Virology. 1982 Apr 15;118(1):202–213. doi: 10.1016/0042-6822(82)90333-6. [DOI] [PubMed] [Google Scholar]
  24. Rowe W. P. Leukemia virus genomes in the chromosomal DNA of the mouse. Harvey Lect. 1978;71:173–192. [PubMed] [Google Scholar]
  25. Salzberg S., Levi Z., Aboud M., Goldberger A. Isolation and characterization of DNA-DNA and DNA-RNA. Biochemistry. 1977 Jan 11;16(1):25–29. doi: 10.1021/bi00620a004. [DOI] [PubMed] [Google Scholar]
  26. Shank P. R., Varmus H. E. Virus-specific DNA in the cytoplasm of avian sarcoma virus-infected cells is a precursor to covalently closed circular viral DNA in the nucleus. J Virol. 1978 Jan;25(1):104–104. doi: 10.1128/jvi.25.1.104-104.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Weinberg R. A. Structure of the intermediates leading to the integrated provirus. Biochim Biophys Acta. 1977 Mar 21;473(1):39–55. doi: 10.1016/0304-419x(77)90006-3. [DOI] [PubMed] [Google Scholar]
  28. Yang W. K., Kiggans J. O., Yang D. M., Ou C. Y., Tennant R. W., Brown A., Bassin R. H. Synthesis and circularization of N- and B-tropic retroviral DNA Fv-1 permissive and restrictive mouse cells. Proc Natl Acad Sci U S A. 1980 May;77(5):2994–2998. doi: 10.1073/pnas.77.5.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yang W. K., Yang D. M., Kiggans J. O., Jr Covalently closed circular DNAs of murine type C retrovirus: depressed formation in cells treated with cycloheximide early after infection. J Virol. 1980 Oct;36(1):181–188. doi: 10.1128/jvi.36.1.181-188.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yoshimura F. K., Weinberg R. A. Restriction endonuclease cleavage of linear and closed circular murine leukemia viral DNAs: discovery of a smaller circular form. Cell. 1979 Feb;16(2):323–332. doi: 10.1016/0092-8674(79)90009-6. [DOI] [PubMed] [Google Scholar]

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