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. 1987 Nov;84(21):7408–7412. doi: 10.1073/pnas.84.21.7408

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.

J D Mosca 1, D P Bednarik 1, N B Raj 1, C A Rosen 1, J G Sodroski 1, W A Haseltine 1, G S Hayward 1, P M Pitha 1
PMCID: PMC299305  PMID: 2823260

Abstract

Herpes simplex virus 1 (HSV-1) infection induces transcription of the chloramphenicol acetyltransferase (CAT) gene directed by the long terminal repeat (LTR) of human immunodeficiency virus (HIV) in both transiently and permanently transfected cells containing the HIV-LTR/CAT hybrid gene. To define the mechanism by which HSV-1 stimulates the HIV LTR, we examined the effects of isolated regulatory genes from HSV-1. The results of cotransfection assays with the immediate-early (IE) genes of HSV-1, IE110 (ICP0) and IE175 (ICP4), showed that the IE110 protein, either alone or in combination with the IE175 protein, can activate the HIV LTR. Cotransfection with the IE175 gene alone or with the Vmw65 gene (coding for a virion transcription factor) alone did not lead to HIV-LTR activation. The lack of requirement for the IE175 or Vmw65 gene products in transient-expression assays was confirmed in permanent cell lines containing the HIV-LTR/CAT hybrid gene by using temperature-sensitive mutants defective in the IE175 gene product or in uncoating functions. By deletion analysis, we localized a 73-bp-long region (positions -104 to -32) from the HIV LTR that responded to HSV-1 activation; when this region, which is distinct from the previously identified trans-activating responsive (TAR) region, was ligated to a heterologous, HSV-1-nonresponsive gene (alpha 4-interferon/CAT), it conferred inducibility by both HSV-1 infection and IE110/175 cotransfection. Both simian and human cytomegalovirus also induced the HIV-LTR/CAT hybrid gene. However, we failed to detect specific upstream sequence requirements for induction by cytomegalovirus. Our results indicate that infection with unrelated viruses can alter the expression of HIV in an infected cell.

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Selected References

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  1. Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Campbell M. E., Palfreyman J. W., Preston C. M. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J Mol Biol. 1984 Nov 25;180(1):1–19. doi: 10.1016/0022-2836(84)90427-3. [DOI] [PubMed] [Google Scholar]
  3. Everett R. D. A detailed analysis of an HSV-1 early promoter: sequences involved in trans-activation by viral immediate-early gene products are not early-gene specific. Nucleic Acids Res. 1984 Apr 11;12(7):3037–3056. doi: 10.1093/nar/12.7.3037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Everett R. D. Activation of cellular promoters during herpes virus infection of biochemically transformed cells. EMBO J. 1985 Aug;4(8):1973–1980. doi: 10.1002/j.1460-2075.1985.tb03880.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Everett R. D. Trans activation of transcription by herpes virus products: requirement for two HSV-1 immediate-early polypeptides for maximum activity. EMBO J. 1984 Dec 20;3(13):3135–3141. doi: 10.1002/j.1460-2075.1984.tb02270.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fauci A. S. Current issues in developing a strategy for dealing with the acquired immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9278–9283. doi: 10.1073/pnas.83.24.9278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Gidoni D., Dynan W. S., Tjian R. Multiple specific contacts between a mammalian transcription factor and its cognate promoters. 1984 Nov 29-Dec 5Nature. 312(5993):409–413. doi: 10.1038/312409a0. [DOI] [PubMed] [Google Scholar]
  9. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jeang K. T., Hayward G. S. A cytomegalovirus DNA sequence containing tracts of tandemly repeated CA dinucleotides hybridizes to highly repetitive dispersed elements in mammalian cell genomes. Mol Cell Biol. 1983 Aug;3(8):1389–1402. doi: 10.1128/mcb.3.8.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  12. Jones K. A., Tjian R. Sp1 binds to promoter sequences and activates herpes simplex virus 'immediate-early' gene transcription in vitro. Nature. 1985 Sep 12;317(6033):179–182. doi: 10.1038/317179a0. [DOI] [PubMed] [Google Scholar]
  13. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  14. Kelley K. A., Pitha P. M. Characterization of a mouse interferon gene locus II. Differential expression of alpha-interferon genes. Nucleic Acids Res. 1985 Feb 11;13(3):825–839. doi: 10.1093/nar/13.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Mosca J. D., Reyes G. R., Pitha P. M., Hayward G. S. Differential activation of hybrid genes containing herpes simplex virus immediate-early or delayed-early promoters after superinfection of stable DNA-transfected cell lines. J Virol. 1985 Dec;56(3):867–878. doi: 10.1128/jvi.56.3.867-878.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Polk B. F., Fox R., Brookmeyer R., Kanchanaraksa S., Kaslow R., Visscher B., Rinaldo C., Phair J. Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men. N Engl J Med. 1987 Jan 8;316(2):61–66. doi: 10.1056/NEJM198701083160201. [DOI] [PubMed] [Google Scholar]
  21. Preston C. M. Abnormal properties of an immediate early polypeptide in cells infected with the herpes simplex virus type 1 mutant tsK. J Virol. 1979 Nov;32(2):357–369. doi: 10.1128/jvi.32.2.357-369.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Rando R. F., Pellett P. E., Luciw P. A., Bohan C. A., Srinivasan A. Transactivation of human immunodeficiency virus by herpesviruses. Oncogene. 1987 Mar;1(1):13–18. [PubMed] [Google Scholar]
  24. 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]
  25. Watson R. J., Clements J. B. A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature. 1980 May 29;285(5763):329–330. doi: 10.1038/285329a0. [DOI] [PubMed] [Google Scholar]

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