Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jan 9;93(1):383–387. doi: 10.1073/pnas.93.1.383

Inhibition of human immunodeficiency virus type 1 and vaccinia virus infection by a dominant negative factor of the interferon regulatory factor family expressed in monocytic cells.

A M Thornton 1, R M Buller 1, A L DeVico 1, I M Wang 1, K Ozato 1
PMCID: PMC40242  PMID: 8552643

Abstract

ICSBP is a member of the interferon (IFN) regulatory factor (IRF) family that regulates expression of type I interferon (IFN) and IFN-regulated genes. To study the role of the IRF family in viral infection, a cDNA for the DNA-binding domain (DBD) of ICSBP was stably transfected into U937 human monocytic cells. Clones that expressed DBD exhibited a dominant negative phenotype and did not elicit antiviral activity against vesicular stomatitis virus (VSV) infection upon IFN treatment. Most notably, cells expressing DBD were refractory to infection by vaccinia virus (VV) and human immunodeficiency virus type 1 (HIV-1). The inhibition of VV infection was attributed to defective virion assembly, and that of HIV-1 to low CD4 expression and inhibition of viral transcription in DBD clones. HIV-1 and VV were found to have sequences in their regulatory regions similar to the IFN-stimulated response element (ISRE) to which IRF family proteins bind. Accordingly, these viral sequences and a cellular ISRE bound a shared factor(s) expressed in U937 cells. These observations suggest a novel host-virus relationship in which the productive infection of some viruses is regulated by the IRF-dependent transcription pathway through the ISRE.

Full text

PDF

Images in this article

385Fig. 2
on p.385
386Fig. 3
on p.386
386Fig. 4
on p.386

Selected References

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

  1. Bovolenta C., Driggers P. H., Marks M. S., Medin J. A., Politis A. D., Vogel S. N., Levy D. E., Sakaguchi K., Appella E., Coligan J. E. Molecular interactions between interferon consensus sequence binding protein and members of the interferon regulatory factor family. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5046–5050. doi: 10.1073/pnas.91.11.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bovolenta C., Lou J., Kanno Y., Park B. K., Thornton A. M., Coligan J. E., Schubert M., Ozato K. Vesicular stomatitis virus infection induces a nuclear DNA-binding factor specific for the interferon-stimulated response element. J Virol. 1995 Jul;69(7):4173–4181. doi: 10.1128/jvi.69.7.4173-4181.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buller R. M., Palumbo G. J. Poxvirus pathogenesis. Microbiol Rev. 1991 Mar;55(1):80–122. doi: 10.1128/mr.55.1.80-122.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chang H. W., Watson J. C., Jacobs B. L. The E3L gene of vaccinia virus encodes an inhibitor of the interferon-induced, double-stranded RNA-dependent protein kinase. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4825–4829. doi: 10.1073/pnas.89.11.4825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen W., Drillien R., Spehner D., Buller R. M. In vitro and in vivo study of the ectromelia virus homolog of the vaccinia virus K1L host range gene. Virology. 1993 Oct;196(2):682–693. doi: 10.1006/viro.1993.1525. [DOI] [PubMed] [Google Scholar]
  6. Cullen B. R. Regulation of human immunodeficiency virus replication. Annu Rev Microbiol. 1991;45:219–250. doi: 10.1146/annurev.mi.45.100191.001251. [DOI] [PubMed] [Google Scholar]
  7. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  8. De Harven E., Yohn D. S. The fine structure of the Yaba monkey tumor poxvirus. Cancer Res. 1966 May;26(5):995–1008. [PubMed] [Google Scholar]
  9. DeVico A. L., Rahman R., Welch J., Crowley R., Lusso P., Sarngadharan M. G., Pal R. Monoclonal antibodies raised against covalently crosslinked complexes of human immunodeficiency virus type 1 gp120 and CD4 receptor identify a novel complex-dependent epitope on gp 120. Virology. 1995 Aug 20;211(2):583–588. doi: 10.1006/viro.1995.1441. [DOI] [PubMed] [Google Scholar]
  10. Driggers P. H., Ennist D. L., Gleason S. L., Mak W. H., Marks M. S., Levi B. Z., Flanagan J. R., Appella E., Ozato K. An interferon gamma-regulated protein that binds the interferon-inducible enhancer element of major histocompatibility complex class I genes. Proc Natl Acad Sci U S A. 1990 May;87(10):3743–3747. doi: 10.1073/pnas.87.10.3743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gendelman H. E., Friedman R. M., Joe S., Baca L. M., Turpin J. A., Dveksler G., Meltzer M. S., Dieffenbach C. A selective defect of interferon alpha production in human immunodeficiency virus-infected monocytes. J Exp Med. 1990 Nov 1;172(5):1433–1442. doi: 10.1084/jem.172.5.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gunnery S., Rice A. P., Robertson H. D., Mathews M. B. Tat-responsive region RNA of human immunodeficiency virus 1 can prevent activation of the double-stranded-RNA-activated protein kinase. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8687–8691. doi: 10.1073/pnas.87.22.8687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989 Aug 25;58(4):729–739. doi: 10.1016/0092-8674(89)90107-4. [DOI] [PubMed] [Google Scholar]
  14. Karupiah G., Xie Q. W., Buller R. M., Nathan C., Duarte C., MacMicking J. D. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science. 1993 Sep 10;261(5127):1445–1448. doi: 10.1126/science.7690156. [DOI] [PubMed] [Google Scholar]
  15. Kimura T., Nakayama K., Penninger J., Kitagawa M., Harada H., Matsuyama T., Tanaka N., Kamijo R., Vilcek J., Mak T. W. Involvement of the IRF-1 transcription factor in antiviral responses to interferons. Science. 1994 Jun 24;264(5167):1921–1924. doi: 10.1126/science.8009222. [DOI] [PubMed] [Google Scholar]
  16. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  17. Marcus P. I., Engelhardt D. L., Hunt J. M., Sekellick M. J. Interferon action: inhibition of vesicular stomatitis virus RNA synthesis induced by virion-bound polymerase. Science. 1971 Nov 5;174(4009):593–598. doi: 10.1126/science.174.4009.593. [DOI] [PubMed] [Google Scholar]
  18. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  19. Moyer R. W. The role of the host cell nucleus in vaccinia virus morphogenesis. Virus Res. 1987 Sep;8(3):173–191. doi: 10.1016/0168-1702(87)90014-1. [DOI] [PubMed] [Google Scholar]
  20. Nelson N., Marks M. S., Driggers P. H., Ozato K. Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription. Mol Cell Biol. 1993 Jan;13(1):588–599. doi: 10.1128/mcb.13.1.588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pine R. Constitutive expression of an ISGF2/IRF1 transgene leads to interferon-independent activation of interferon-inducible genes and resistance to virus infection. J Virol. 1992 Jul;66(7):4470–4478. doi: 10.1128/jvi.66.7.4470-4478.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pomerantz R. J., Hirsch M. S. Interferon and human immunodeficiency virus infection. Interferon. 1987;9:113–127. [PubMed] [Google Scholar]
  23. Roseman N. A., Slabaugh M. B. The vaccinia virus HindIII F fragment: nucleotide sequence of the left 6.2 kb. Virology. 1990 Oct;178(2):410–418. doi: 10.1016/0042-6822(90)90338-r. [DOI] [PubMed] [Google Scholar]
  24. Roy S., Katze M. G., Parkin N. T., Edery I., Hovanessian A. G., Sonenberg N. Control of the interferon-induced 68-kilodalton protein kinase by the HIV-1 tat gene product. Science. 1990 Mar 9;247(4947):1216–1219. doi: 10.1126/science.2180064. [DOI] [PubMed] [Google Scholar]
  25. Salmon P., Giovane A., Wasylyk B., Klatzmann D. Characterization of the human CD4 gene promoter: transcription from the CD4 gene core promoter is tissue-specific and is activated by Ets proteins. Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7739–7743. doi: 10.1073/pnas.90.16.7739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schmelz M., Sodeik B., Ericsson M., Wolffe E. J., Shida H., Hiller G., Griffiths G. Assembly of vaccinia virus: the second wrapping cisterna is derived from the trans Golgi network. J Virol. 1994 Jan;68(1):130–147. doi: 10.1128/jvi.68.1.130-147.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smith G. L. Virus strategies for evasion of the host response to infection. Trends Microbiol. 1994 Mar;2(3):81–88. doi: 10.1016/0966-842x(94)90539-8. [DOI] [PubMed] [Google Scholar]
  28. Sperber S. J., Gocke D. J., Haberzettl C., Kuk R., Schwartz B., Pestka S. Anti-HIV-1 activity of recombinant and hybrid species of interferon-alpha. J Interferon Res. 1992 Oct;12(5):363–368. doi: 10.1089/jir.1992.12.363. [DOI] [PubMed] [Google Scholar]
  29. Veals S. A., Schindler C., Leonard D., Fu X. Y., Aebersold R., Darnell J. E., Jr, Levy D. E. Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol Cell Biol. 1992 Aug;12(8):3315–3324. doi: 10.1128/mcb.12.8.3315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. el Kharroubi A., Verdin E. Protein-DNA interactions within DNase I-hypersensitive sites located downstream of the HIV-1 promoter. J Biol Chem. 1994 Aug 5;269(31):19916–19924. [PubMed] [Google Scholar]
  31. van Gemen B., van Beuningen R., Nabbe A., van Strijp D., Jurriaans S., Lens P., Kievits T. A one-tube quantitative HIV-1 RNA NASBA nucleic acid amplification assay using electrochemiluminescent (ECL) labelled probes. J Virol Methods. 1994 Sep;49(2):157–167. doi: 10.1016/0166-0934(94)90040-x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES