Herpesvirus Trans-Activation of Human Immunodeficiency Virus Type-1

  • Joseph D. Mosca
Conference paper


In humans, HIV-1 infection is characterized by a period of latency followed by progression to acquired immunodeficiency syndrome (AIDS) and AIDS-related complex in some cases (Blattner et al. 1985). Factors that influence HIV-1 latency are poorly understood. Several models have been proposed that might explain. how HIV-1, when persisting in the latent form, can be induced by physiochemical stimuli and expressed as infectious virus particles (Folks et al. 1986). These models include transcriptional repression of integrated proviral DNA by DNA-binding proteins, chromatin conformation, and DNA hypermethylation. To understand these processes, permanent cell lines were constructed that contained as a reporter gene the bacterial chloramphenicol acetyltransferase (CAT) gene coding region fused to the HIV-1-LTR (pU3R-III-CAT) or human T leukemia virus (HTLV) type I (HTLV-I)-LTR (pU3R-I-CAT) promoter sequences. In these permanent cell lines HIV-1-LTR but not HTLV-I-LTR expression was suppressed when integrated into the host chromatin (Mosca et al. 1987a). We have provided evidence that the suppression of HIV-1-LTR expression is accompanied by methylation of LTR sequences (Bednarik et al. 1987). Using these permanent cell lines as a model system that appears to mimic the latent integrated HIV-1 provirus, we showed that reactivation of the reporter CAT gene initiated from the HIV-1-LTR can be induced by either treatment with a protein synthesis inhibitor (cycloheximide) or infection with herpesviruses (Mosca et al. 1987a). For herpes simplex virus I (HSV-1), we have identified the 5’ upstream sequence within the HIV-1-LTR that appears to contain a specific recognition site necessary for the activation by HSV-1 and by the HSV-1 encoded IE110 (ICPO) regulatory protein (Mosca et al. 1987b). However, for reactivation of the HIV-1-LTR by cytomegalovirus (CMV), no specific recognition sequence within the HIV-1-LTR could be found, indicating that different molecular mechanisms exist for HIV-1-LTR activation by HSV-1 and CMV.


Human Immunodeficiency Virus Herpes Simplex Virus Type Permanent Cell Line IE175 Protein Specific Recognition Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Batterson N, Roizman B (1983) Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol 46: 371–377.PubMedGoogle Scholar
  2. Bednarik DP, Mosca JD, Raj NBK (1987) Methylation as a modulator of ex- pression of human immunodeficiency virus. J Virol 61: 1253–1257.PubMedGoogle Scholar
  3. Blattner WA, Biggar RJ, Weiss SW, Melbye M, Goedert JJ (1985) Epidemiology of human T-lymphotropic virus type III and the risk of the acquired immunodeficiency syndrome. Ann Intern Med 103: 665–669.PubMedCrossRefGoogle Scholar
  4. Campbell MEM, Palfreyman JW, Preston C (1984) Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J MolGoogle Scholar
  5. Cedar H (1984) DNA methylation and gene expression. In: Razin A, Cedar H, Riggs AD (eds.) DNA Methylation: Biochemistry and Biological Significance. Springer-Verlag, New York, pp 147–164.CrossRefGoogle Scholar
  6. Doerfler W (1983) DNA methylation and gene activity. Ann Rev BiochemGoogle Scholar
  7. Doerfler W (1984) DNA methylation and its functional significance: studies on the adenovirus system. Curr Top Microbiol Immunol 108: 79–98.PubMedCrossRefGoogle Scholar
  8. Folks T, Powell DM, Lightfoote MM, Benn S, Martin MA, Fauci AS (1986) Induction of HTLV-III/LAV from a nonvirus-producing T-cell line; implications for latency. Science 231: 600–602.PubMedCrossRefGoogle Scholar
  9. Jones PA (1985) Altering gene expression with 5-azacytidine. Cell 40:485Keshet I, Hurwitz-Lieman J, Cedar H (1986) DNA methylation affects the formation of active chromatin. Cell 44: 535–543.Google Scholar
  10. Kirchner H (1982) Immunobiology of infections with herpes simplex virus. In: Melnick JL (ed), Monogram Virology Vol 13, pp 1–104.Google Scholar
  11. Mosca JD, Reyes GR, Pitha PM, Hayward GS (1985) 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 56: 867–878.PubMedGoogle Scholar
  12. Mosca JD, Bednarik DP, Raj NBBK, Rosen CA, Sodroski JG, Haseltine WA, Pitha PM (1987a) Herpes simplex virus type-1 can reactivate transcription of latent human immunodeficiency virus. Nature (London) 325: 67–70.CrossRefGoogle Scholar
  13. Mosca JD, Bednarik DP, Raj NBK, Rosen CA, Sodroski JG, Haseltine WA, Hayward GS, Pitha PM (1987b) Activation of human immunodeficiency virus by herpes virus infection: Identification of a region within the long terminal repeat that responds to a transacting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci USA 84: 7408–7412.PubMedCrossRefGoogle Scholar
  14. Nabel G, Baltimore D (1987) An inducible transcription factor activates expression of human immunodeficiency virus in T-cells. Nature (London) 326: 711–713.CrossRefGoogle Scholar
  15. Nyce J, Linn L, Jones PA (1986) Variable effects of DNA-synthesis inhibitors upon DNA methylation in mammalian cells. Nucleic Acids Res 14: 4353–4367.PubMedCrossRefGoogle Scholar
  16. O’Hare P, Hayward GS (1984) Expression of recombinant genes containing herpes simplex virus delayed-early and immediate-early regulatory regions and transactivation by herpesvirus infection. J Virol 52: 522531.Google Scholar
  17. Preston CM (1979) Abnormal properties of an immediate-early polypeptide in cells infected with the herpes simplex virus type 1 mutant tsk. J Virol 32: 357–369.PubMedGoogle Scholar
  18. Quinn TC, Piot P, McCormick JB, Feinsod FM, Taelman H, Kapita B, Stevens W, Fauci AS (1987) Serologic and immunologic studies in patients with AIDS in North American and African. The potential role of infectious agents as cofactors in human immunodeficiency virus infection. JAMAGoogle Scholar
  19. Raj NBK, Pitha PM (1983) Two levels of regulation of beta-interferon gene expression in human cells. Proc Natl Acad Sci USA 80: 3923–3927.PubMedCrossRefGoogle Scholar
  20. Rosen CA, Sodroski JB, Haseltine WA (1985) The location of cis-acting regulatory sequences in the human T-cell lymphotropic virus type III ( HTLV-III/LAV) long terminal repeat. Cell 41: 813–823.Google Scholar
  21. Watson RJ, Clements JB (1980) A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature (London) 285: 329–330.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Joseph D. Mosca
    • 1
    • 2
  1. 1.Henry M. Jackson FoundationRockvilleUSA
  2. 2.Department of Immunology and Infectious DiseasesThe Johns Hopkins University School of Public HealthBaltimoreUSA

Personalised recommendations