• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jvirolPermissionsJournals.ASM.orgJournalJV ArticleJournal InfoAuthorsReviewers
J Virol. Apr 1987; 61(4): 1253–1257.
PMCID: PMC254089

Methylation as a modulator of expression of human immunodeficiency virus.

Abstract

When Vero or murine cells were stably transfected with the human immunodeficiency virus (HIV) long terminal repeat (LTR) that directs the chloramphenicol acetyltransferase (CAT) gene (pU3R-III-CAT), expression was suppressed. Treatment with the nucleoside analog 5-azacytidine (5-azaC) restored CAT expression. S1 nuclease analysis and a nuclear run-on assay demonstrated that activation of the latent HIV LTR by 5-azacytidine occurred at the transcriptional level. Southern blot analysis demonstrated that this activation was due to the demethylation of cytosine residues in the LTR enhancer. Thus, the HIV LTR appears to be susceptible to transcriptional inactivation by methylation, a process that is proposed to play a modulatory role in viral latency.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adachi A, Gendelman HE, Koenig S, Folks T, Willey R, Rabson A, Martin MA. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. [PMC free article] [PubMed]
  • Arya SK, Guo C, Josephs SF, Wong-Staal F. Trans-activator gene of human T-lymphotropic virus type III (HTLV-III). Science. 1985 Jul 5;229(4708):69–73. [PubMed]
  • Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vézinet-Brun F, Rouzioux C, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):868–871. [PubMed]
  • Bird AP. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. [PubMed]
  • Blattner WA, Biggar RJ, Weiss SH, Melbye M, Goedert JJ. Epidemiology of human T-lymphotropic virus type III and the risk of the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):665–670. [PubMed]
  • Blin N, Stafford DW. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. [PMC free article] [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Cullen BR. Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell. 1986 Sep 26;46(7):973–982. [PubMed]
  • Dayton AI, Sodroski JG, Rosen CA, Goh WC, Haseltine WA. 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. [PubMed]
  • Dobritsa AP, Dobritsa SV. DNA protection with the DNA methylase M . BbvI from Bacillus brevis var. GB against cleavage by the restriction endonucleases PstI and PvuII. Gene. 1980 Jul;10(2):105–112. [PubMed]
  • Doerfler W. DNA methylation and gene activity. Annu Rev Biochem. 1983;52:93–124. [PubMed]
  • Doerfler W. DNA methylation and its functional significance: studies on the adenovirus system. Curr Top Microbiol Immunol. 1984;108:79–98. [PubMed]
  • Fahey JL, Prince H, Weaver M, Groopman J, Visscher B, Schwartz K, Detels R. Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders. Am J Med. 1984 Jan;76(1):95–100. [PubMed]
  • Feinberg MB, Jarrett RF, Aldovini A, Gallo RC, Wong-Staal F. HTLV-III expression and production involve complex regulation at the levels of splicing and translation of viral RNA. Cell. 1986 Sep 12;46(6):807–817. [PubMed]
  • Folks T, Powell DM, Lightfoote MM, Benn S, Martin MA, Fauci AS. Induction of HTLV-III/LAV from a nonvirus-producing T-cell line: implications for latency. Science. 1986 Feb 7;231(4738):600–602. [PubMed]
  • Harada S, Koyanagi Y, Yamamoto N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science. 1985 Aug 9;229(4713):563–566. [PubMed]
  • Harbers K, Schnieke A, Stuhlmann H, Jähner D, Jaenisch R. DNA methylation and gene expression: endogenous retroviral genome becomes infectious after molecular cloning. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7609–7613. [PMC free article] [PubMed]
  • Haseltine WA, Sodroski J, Rosen C. The lor gene and pathogenesis of HTLV-I, -II, and -III. Cancer Res. 1985 Sep;45(9 Suppl):4545s–4549s. [PubMed]
  • Hoxie JA, Haggarty BS, Rackowski JL, Pillsbury N, Levy JA. Persistent noncytopathic infection of normal human T lymphocytes with AIDS-associated retrovirus. Science. 1985 Sep 27;229(4720):1400–1402. [PubMed]
  • Jones PA. Altering gene expression with 5-azacytidine. Cell. 1985 Mar;40(3):485–486. [PubMed]
  • Keshet I, Lieman-Hurwitz J, Cedar H. DNA methylation affects the formation of active chromatin. Cell. 1986 Feb 28;44(4):535–543. [PubMed]
  • Klatzmann D, Barré-Sinoussi F, Nugeyre MT, Danquet C, Vilmer E, Griscelli C, Brun-Veziret F, Rouzioux C, Gluckman JC, Chermann JC, et al. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. [PubMed]
  • Kruczek I, Doerfler W. Expression of the chloramphenicol acetyltransferase gene in mammalian cells under the control of adenovirus type 12 promoters: effect of promoter methylation on gene expression. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7586–7590. [PMC free article] [PubMed]
  • Mantei N, Boll W, Weissmann C. Rabbit beta-globin mRNA production in mouse L cells transformed with cloned rabbit beta-globin chromosomal DNA. Nature. 1979 Sep 6;281(5726):40–46. [PubMed]
  • Manzari V, Wong-Staal F, Franchini G, Colombini S, Gelmann EP, Oroszlan S, Staal S, Gallo RC. Human T-cell leukemia-lymphoma virus (HTLV): cloning of an integrated defective provirus and flanking cellular sequences. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1574–1578. [PMC free article] [PubMed]
  • Mosca JD, Bednarik DP, Raj NB, Rosen CA, Sodroski JG, Haseltine WA, Pitha PM. Herpes simplex virus type-1 can reactivate transcription of latent human immunodeficiency virus. Nature. 1987 Jan 1;325(6099):67–70. [PubMed]
  • Mosca JD, Reyes GR, Pitha PM, Hayward GS. 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. [PMC free article] [PubMed]
  • Nyce J, Liu L, Jones PA. Variable effects of DNA-synthesis inhibitors upon DNA methylation in mammalian cells. Nucleic Acids Res. 1986 May 27;14(10):4353–4367. [PMC free article] [PubMed]
  • Popovic M, Sarngadharan MG, Read E, Gallo RC. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. [PubMed]
  • Queen C, Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. [PubMed]
  • Raj NB, Pitha PM. 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. [PMC free article] [PubMed]
  • Rigby PW, Dieckmann M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. [PubMed]
  • Rosen CA, Sodroski JG, Goh WC, Dayton AI, Lippke J, Haseltine WA. Post-transcriptional regulation accounts for the trans-activation of the human T-lymphotropic virus type III. Nature. 1986 Feb 13;319(6054):555–559. [PubMed]
  • Rosen CA, Sodroski JG, Haseltine WA. 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. [PubMed]
  • Sodroski J, Patarca R, Rosen C, Wong-Staal F, Haseltine W. Location of the trans-activating region on the genome of human T-cell lymphotropic virus type III. Science. 1985 Jul 5;229(4708):74–77. [PubMed]
  • Sodroski JG, Rosen CA, Haseltine WA. Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells. Science. 1984 Jul 27;225(4660):381–385. [PubMed]
  • Sodroski J, Rosen C, Wong-Staal F, Salahuddin SZ, Popovic M, Arya S, Gallo RC, Haseltine WA. Trans-acting transcriptional regulation of human T-cell leukemia virus type III long terminal repeat. Science. 1985 Jan 11;227(4683):171–173. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Vilmer E, Barre-Sinoussi F, Rouzioux C, Gazengel C, Brun FV, Dauguet C, Fischer A, Manigne P, Chermann JC, Griscelli C, et al. Isolation of new lymphotropic retrovirus from two siblings with haemophilia B, one with AIDS. Lancet. 1984 Apr 7;1(8380):753–757. [PubMed]
  • Zagury D, Bernard J, Leonard R, Cheynier R, Feldman M, Sarin PS, Gallo RC. Long-term cultures of HTLV-III--infected T cells: a model of cytopathology of T-cell depletion in AIDS. Science. 1986 Feb 21;231(4740):850–853. [PubMed]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles