The Role of a Repetitive Palindromic Sequence Element in the Human Cytomegalovirus Major Immediate Early Enhancer

Fickenscher, Helmut; Stamminger, Thomas; Rüger, Rüdiger; Fleckenstein, Bernhard

doi:10.1099/0022-1317-70-1-107

Cited by 54 publications

(51 citation statements)

References 82 publications

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“…Plasmid pFJ3, containing the flgalactosidase gene controlled by simian virus 40 promoter and enhancer sequences was kindly provided by Dr F. J. Rixon. Plasmid pRR55, containing the CAT gene under the control of human cytomegalovirus (HCMV) strain AD169 IE gene promoter and enhancer sequences (Fickenscher et al, 1989), was kindly provided by Dr R. Rfiger. Plasmid pIE3CAT, containing the CAT gene under HSV-1 IE gene 3 control (Stow et al, 1986), was kindly supplied by Dr T. Paterson.…”

Section: Methodsmentioning

confidence: 99%

Control of expression of the varicella-zoster virus major immediate early gene

Mckee

Disney²,

Everett³

et al. 1990

Journal of General Virology

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The cis-acting DNA sequences and trans-acting proteins that control the expression of the major immediate early (IE) gene of varicella-zoster virus (VZV) were investigated. The location of the IE mRNA 5' terminus was determined by primer extension and S1 nuclease analyses and the functional activities of DNA sequences upstream of this site were analysed by a transfection assay. The VZV IE promoter exhibited low activity in BHK and HeLa cells, but was transactivated by the herpes simplex virus type 1 (HSV-1) virion protein Vmw65. DNA sequences between positions -131 and +57 were responsible for promoter activity, whereas sequences between -410 and -131 mediated the response to Vmw65. Two short elements in the -410 to -131 region formed protein-DNA complexes with HeLa cell nuclear proteins and formed a ternary complex when Vmw65 was added. One of the elements, ATGTAAATGAAAT, possessed a strong similarity to the HSV-1 TAATGARAT. The VZV homologue of Vmw65, encoded by open reading frame (ORF) 10, failed to trans-activate expression from HSV-1 or VZV IE promoters and did not form a ternary complex with functional TAATGARAT elements and HeLa cell proteins. Therefore, stimulation of VZV IE transcription by Vmw65 can occur by a mechanism similar to that employed by HSV-1, but VZV ORF 10 does not function as a trans-activator of IE gene expression.

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Section: Methodsmentioning

confidence: 99%

Control of expression of the varicella-zoster virus major immediate early gene

Mckee

Disney²,

Everett³

et al. 1990

Journal of General Virology

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show abstract

“…These features are consistent with the model of a large nucleoprotein complex forming on the enhancer sequence and allowing for extensive protein-protein interactions. To investigate the functional role of different repeat elements, competition assays were performed both in vivo (Fickenscher et al, 1989) and in vitro (Ghazal et al, 1988a), in which synthetic oligonucleotides corresponding to repeat elements competed for factors of the transcriptional machinery. It was shown that competition with the 18 and 19 bp element efficiently diminished the stimulatory effect of the HCMV enhancer on transcription.…”

Section: Regulatory Elements In the Ie1 Upstream Regionmentioning

confidence: 99%

Human Cytomegalovirus: Recent Aspects from Molecular Biology

Mach

Stamminger

Jahn

1989

Journal of General Virology

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“…16 In the present study, we evaluated the ability of 8 Br-cAMP to enhance DNA-vaccine-induced immune responses to the HIV-1 Env product derived from the expression cassette controlled by the CMV promoter, which is known to be easily up-regulated by an elevation in the level of intracellular cAMP. 17 The major enhancer of human cytomegalovirus (CMV) has been shown to exert a strong constitutive activity in a wide variety of cell types. 18,19 An 8 bp core palindrome was shown to be capable of acting as a cAMP-responsive element (CRE).…”

Section: Introductionmentioning

confidence: 99%

“…18,19 An 8 bp core palindrome was shown to be capable of acting as a cAMP-responsive element (CRE). 17 Elevation in intracellular concentrations of cAMP, a second messenger, results in the upregulation of CRE and enhancement of the transcriptional activity of the CMV promoter. Based on these findings, we tested the ability of 8 Br-cAMP to enhance the immune response induced by intramuscular (i.m.)…”

Section: Introductionmentioning

confidence: 99%

8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine

Arai

Hamajima

et al. 2000

Gene Ther

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From a series of preclinical studies and animal experiments, we have been able to demonstrate that DNA vaccines are a promising tool in strategies for protecting hosts from a variety of infectious diseases. Since the promoter activity of the human cytomegalovirus immediate-early promoter/ enhancer (CMV promoter) is known to be responsive to an elevation in the level of intracellular cAMP, we hypothesized that use of cAMP analogue (8-Bromo adenosine 3Ј5Ј-cyclic monophosphate, 8 Br-cAMP) would increase the level of transgene expression supported by the CMV, and enhance the ability of DNA vaccines to evoke an immune response against the transgene product in vivo. To evaluate this hypothesis, immune responses against HIV-1 envelope protein, gp160, an immunogenic HIV-1 component expressed under the control of the CMV promoter, were evaluated in BALB/c mice with or without stimulation by 8 Br-cAMP. DNA vaccine with 8 Br-cAMP was intramuscularly (i.m.) or intranasally (i.n.) administered to BALB/c mice twice on days 0 and 14. Regardless of which route was used, the combination increased the serum IgG antibody (Ab) titer, HIV-1-

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The Role of a Repetitive Palindromic Sequence Element in the Human Cytomegalovirus Major Immediate Early Enhancer

Cited by 54 publications

References 82 publications

Control of expression of the varicella-zoster virus major immediate early gene

Control of expression of the varicella-zoster virus major immediate early gene

Human Cytomegalovirus: Recent Aspects from Molecular Biology

8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine

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