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
. 1991 Nov 1;88(21):9573–9577. doi: 10.1073/pnas.88.21.9573

Inhibition by interferon of herpes simplex virus type 1-activated transcription of tat-defective provirus.

W Popik 1, P M Pitha 1
PMCID: PMC52760  PMID: 1719535

Abstract

The herpes simplex virus type 1 (HSV-1)-mediated transactivation of human immunodeficiency virus type 1 (HIV-1) provirus was studied in cell lines containing either integrated tat-defective HIV-1 provirus (HNHIVdt4 cells) or the tat-defective HIV-1 provirus, and a plasmid in which the expression of human alpha 2 interferon (HuIFN-alpha 2) was under the control of the HIV-1 long terminal repeat (LTR) (HNHIV alpha 1 cells). In both cell lines, transcription of the HIV-1 provirus was below the limits of detection, but it could be induced effectively by transfection with a HIV-1 tat-expression plasmid. In HNHIV alpha 1 cells, HuIFN-alpha 2 was induced concomitantly with HIV-1 provirus, although these cells synthesized only low levels of IFN constitutively. In contrast, infections with HSV-1 activated transcription of HIV-1 provirus only in HNHIVdt4 cells but not in HNHIV alpha 1 cells. Similarly in a transient expression assay, HSV-1 up-regulated expression of a HIV LTR-CAT (chloramphenicol acetyltransferase gene) plasmid in HNHIVdt4 but not in HNHIV alpha 1 cells. No major differences could be detected in the expression of HSV-1 immediate-early (IE) genes IE175 and IE110 (which are essential for the activation of HIV-1 LTR) in HNHIVdt4 and HNHIV alpha 1 cells to account for the inability of HSV-1 to induce HIV-1 in HNHIV alpha 1 cells. However, major differences were observed in the binding pattern of NF-kappa B-specific nuclear proteins to the enhancer region of the HIV-1 LTR: whereas binding of the 45-kDa NF-kappa B-specific nuclear protein was detected in nuclear extracts from HNHIVdt4 cells, no protein binding was seen in extracts from HNHIV alpha 1 cells. These results suggest an alternate mechanism by which IFN may alter the expression of cellular and viral genes.

Full text

PDF
9577

Images in this article

9574Image
on p.9574
9575Image
on p.9575
9575Image
on p.9575
9575Image
on p.9575
9575Image
on p.9575
9575Image
on p.9575
9576Image
on p.9576
9576Image
on p.9576
9576Image
on p.9576

Selected References

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

  1. Albrecht M. A., DeLuca N. A., Byrn R. A., Schaffer P. A., Hammer S. M. The herpes simplex virus immediate-early protein, ICP4, is required to potentiate replication of human immunodeficiency virus in CD4+ lymphocytes. J Virol. 1989 May;63(5):1861–1868. doi: 10.1128/jvi.63.5.1861-1868.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baeuerle P. A., Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988 Oct 28;242(4878):540–546. doi: 10.1126/science.3140380. [DOI] [PubMed] [Google Scholar]
  3. Ballard D. W., Walker W. H., Doerre S., Sista P., Molitor J. A., Dixon E. P., Peffer N. J., Hannink M., Greene W. C. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. Cell. 1990 Nov 16;63(4):803–814. doi: 10.1016/0092-8674(90)90146-6. [DOI] [PubMed] [Google Scholar]
  4. Bandyopadhyay S. K., Kalvakolanu D. V., Sen G. C. Gene induction by interferons: functional complementation between trans-acting factors induced by alpha interferon and gamma interferon. Mol Cell Biol. 1990 Oct;10(10):5055–5063. doi: 10.1128/mcb.10.10.5055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bednarik D. P., Mosca J. D., Raj N. B., Pitha P. M. Inhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated alpha 2-interferon. Proc Natl Acad Sci U S A. 1989 Jul;86(13):4958–4962. doi: 10.1073/pnas.86.13.4958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Clouse K. A., Robbins P. B., Fernie B., Ostrove J. M., Fauci A. S. Viral antigen stimulation of the production of human monokines capable of regulating HIV1 expression. J Immunol. 1989 Jul 15;143(2):470–475. [PubMed] [Google Scholar]
  8. Cullen B. R., Greene W. C. Functions of the auxiliary gene products of the human immunodeficiency virus type 1. Virology. 1990 Sep;178(1):1–5. doi: 10.1016/0042-6822(90)90373-y. [DOI] [PubMed] [Google Scholar]
  9. Dayton A. I., Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986 Mar 28;44(6):941–947. doi: 10.1016/0092-8674(86)90017-6. [DOI] [PubMed] [Google Scholar]
  10. De Stasio P. R., Taylor M. W. Specific effect of interferon on the herpes simplex virus type 1 transactivation event. J Virol. 1990 Jun;64(6):2588–2593. doi: 10.1128/jvi.64.6.2588-2593.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dingwall C., Ernberg I., Gait M. J., Green S. M., Heaphy S., Karn J., Lowe A. D., Singh M., Skinner M. A., Valerio R. Human immunodeficiency virus 1 tat protein binds trans-activation-responsive region (TAR) RNA in vitro. Proc Natl Acad Sci U S A. 1989 Sep;86(18):6925–6929. doi: 10.1073/pnas.86.18.6925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Engelhardt J. F., Kellum M. J., Bisat F., Pitha P. M. Retrovirus vector-targeted inducible expression of human beta-interferon gene to B-cells. Virology. 1990 Oct;178(2):419–428. doi: 10.1016/0042-6822(90)90339-s. [DOI] [PubMed] [Google Scholar]
  14. Felber B. K., Drysdale C. M., Pavlakis G. N. Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein. J Virol. 1990 Aug;64(8):3734–3741. doi: 10.1128/jvi.64.8.3734-3741.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fu X. Y., Kessler D. S., Veals S. A., Levy D. E., Darnell J. E., Jr ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555–8559. doi: 10.1073/pnas.87.21.8555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gendelman H. E., Phelps W., Feigenbaum L., Ostrove J. M., Adachi A., Howley P. M., Khoury G., Ginsberg H. S., Martin M. A. Trans-activation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9759–9763. doi: 10.1073/pnas.83.24.9759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ghosh S., Gifford A. M., Riviere L. R., Tempst P., Nolan G. P., Baltimore D. Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. Cell. 1990 Sep 7;62(5):1019–1029. doi: 10.1016/0092-8674(90)90276-k. [DOI] [PubMed] [Google Scholar]
  18. Gimble J. M., Duh E., Ostrove J. M., Gendelman H. E., Max E. E., Rabson A. B. Activation of the human immunodeficiency virus long terminal repeat by herpes simplex virus type 1 is associated with induction of a nuclear factor that binds to the NF-kappa B/core enhancer sequence. J Virol. 1988 Nov;62(11):4104–4112. doi: 10.1128/jvi.62.11.4104-4112.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Harper H. D., Pitha P. M. Effect of concanavalin A on interferon induction by poly IC. Biochem Biophys Res Commun. 1973 Aug 21;53(4):1220–1226. doi: 10.1016/0006-291x(73)90595-0. [DOI] [PubMed] [Google Scholar]
  21. Imam A. M., Ackrill A. M., Dale T. C., Kerr I. M., Stark G. R. Transcription factors induced by interferons alpha and gamma. Nucleic Acids Res. 1990 Nov 25;18(22):6573–6580. doi: 10.1093/nar/18.22.6573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Klotzbücher A., Mittnacht S., Kirchner H., Jacobsen H. Different effects of IFN gamma and IFN alpha/beta on "immediate early" gene expression of HSV-1. Virology. 1990 Nov;179(1):487–491. doi: 10.1016/0042-6822(90)90322-i. [DOI] [PubMed] [Google Scholar]
  23. LaMarco K. L., McKnight S. L. Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes. Genes Dev. 1989 Sep;3(9):1372–1383. doi: 10.1101/gad.3.9.1372. [DOI] [PubMed] [Google Scholar]
  24. Malim M. H., Hauber J., Fenrick R., Cullen B. R. Immunodeficiency virus rev trans-activator modulates the expression of the viral regulatory genes. Nature. 1988 Sep 8;335(6186):181–183. doi: 10.1038/335181a0. [DOI] [PubMed] [Google Scholar]
  25. Mizoguchi J., Pitha P. M., Raj N. B. Efficient expression in Escherichia coli of two species of human interferon-alpha and their hybrid molecules. DNA. 1985 Jun;4(3):221–232. doi: 10.1089/dna.1985.4.221. [DOI] [PubMed] [Google Scholar]
  26. Molitor J. A., Walker W. H., Doerre S., Ballard D. W., Greene W. C. NF-kappa B: a family of inducible and differentially expressed enhancer-binding proteins in human T cells. Proc Natl Acad Sci U S A. 1990 Dec;87(24):10028–10032. doi: 10.1073/pnas.87.24.10028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mosca J. D., Bednarik D. P., Raj N. B., Pitha P. M. Is there a role for herpesvirus in AIDS? Nature. 1988 Jan 14;331(6152):122–122. doi: 10.1038/331122a0. [DOI] [PubMed] [Google Scholar]
  28. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Hayward G. S., Pitha P. M. Activation of human immunodeficiency virus by herpesvirus infection: identification of a region within the long terminal repeat that responds to a trans-acting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7408–7412. doi: 10.1073/pnas.84.21.7408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mosca J. D., Bednarik D. P., Raj N. B., Rosen C. A., Sodroski J. G., Haseltine W. A., Pitha P. M. Herpes simplex virus type-1 can reactivate transcription of latent human immunodeficiency virus. Nature. 1987 Jan 1;325(6099):67–70. doi: 10.1038/325067a0. [DOI] [PubMed] [Google Scholar]
  30. Nabel G. J., Rice S. A., Knipe D. M., Baltimore D. Alternative mechanisms for activation of human immunodeficiency virus enhancer in T cells. Science. 1988 Mar 11;239(4845):1299–1302. doi: 10.1126/science.2830675. [DOI] [PubMed] [Google Scholar]
  31. O'Hare P., Hayward G. S. Evidence for a direct role for both the 175,000- and 110,000-molecular-weight immediate-early proteins of herpes simplex virus in the transactivation of delayed-early promoters. J Virol. 1985 Mar;53(3):751–760. doi: 10.1128/jvi.53.3.751-760.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Oberman F., Panet A. Inhibition of transcription of herpes simplex virus immediate early genes in interferon-treated human cells. J Gen Virol. 1988 Jun;69(Pt 6):1167–1177. doi: 10.1099/0022-1317-69-6-1167. [DOI] [PubMed] [Google Scholar]
  33. Ostrove J. M., Leonard J., Weck K. E., Rabson A. B., Gendelman H. E. Activation of the human immunodeficiency virus by herpes simplex virus type 1. J Virol. 1987 Dec;61(12):3726–3732. doi: 10.1128/jvi.61.12.3726-3732.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Quinn T. C., Piot P., McCormick J. B., Feinsod F. M., Taelman H., Kapita B., Stevens W., Fauci A. S. Serologic and immunologic studies in patients with AIDS in North America and Africa. The potential role of infectious agents as cofactors in human immunodeficiency virus infection. JAMA. 1987 May 15;257(19):2617–2621. [PubMed] [Google Scholar]
  35. Raj N. B., Engelhardt J., Au W. C., Levy D. E., Pitha P. M. Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation. J Biol Chem. 1989 Oct 5;264(28):16658–16666. [PubMed] [Google Scholar]
  36. Raj N. B., Pitha P. M. Analysis of interferon mRNA in human fibroblast cells induced to produce interferon. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7426–7430. doi: 10.1073/pnas.78.12.7426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Raj N. B., Pitha P. M. Two levels of regulation of beta-interferon gene expression in human cells. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3923–3927. doi: 10.1073/pnas.80.13.3923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Rivière Y., Blank V., Kourilsky P., Israël A. Processing of the precursor of NF-kappa B by the HIV-1 protease during acute infection. Nature. 1991 Apr 18;350(6319):625–626. doi: 10.1038/350625a0. [DOI] [PubMed] [Google Scholar]
  39. Rosen C. A., Pavlakis G. N. Tat and Rev: positive regulators of HIV gene expression. AIDS. 1990 Jun;4(6):499–509. [PubMed] [Google Scholar]
  40. Rosen C. A., Sodroski J. G., Campbell K., Haseltine W. A. Construction of recombinant murine retroviruses that express the human T-cell leukemia virus type II and human T-cell lymphotropic virus type III trans activator genes. J Virol. 1986 Jan;57(1):379–384. doi: 10.1128/jvi.57.1.379-384.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  42. Selby M. J., Bain E. S., Luciw P. A., Peterlin B. M. Structure, sequence, and position of the stem-loop in tar determine transcriptional elongation by tat through the HIV-1 long terminal repeat. Genes Dev. 1989 Apr;3(4):547–558. doi: 10.1101/gad.3.4.547. [DOI] [PubMed] [Google Scholar]
  43. Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26;47(6):921–928. doi: 10.1016/0092-8674(86)90807-x. [DOI] [PubMed] [Google Scholar]
  44. Sharp P. A., Marciniak R. A. HIV TAR: an RNA enhancer? Cell. 1989 Oct 20;59(2):229–230. doi: 10.1016/0092-8674(89)90279-1. [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