Abstract
A major determinant controlling reactivation of persistent viruses is likely to be the level of cellular factors which regulate virus transcription. Human cytomegalovirus (the largest human herpesvirus) does not replicate in human teratocarcinoma (T2) cells due to a block in transcription of immediate early (IE) gene expression, but these cells become permissive upon retinoic acid induced differentiation. We have analysed changes in DNA binding factors to the major IE promoter/regulatory region of HCMV that occur during differentiation of T2 cells to a permissive phenotype. We show that undifferentiated T2 cells contain a specific nuclear factor that binds to a far upstream region of the major IE regulatory region. Differentiation of T2 cells is associated with a major decrease in this factor and deletion of its specific binding site from IE expression vectors also results in increased levels of expression in undifferentiated cells. Consequently, this novel factor present in undifferentiated cells is a candidate for a differentiation specific negative regulator of HCMV IE gene expression which binds to an element upstream of the major IE enhancer.
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- Boshart M., Weber F., Jahn G., Dorsch-Häsler K., Fleckenstein B., Schaffner W. A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell. 1985 Jun;41(2):521–530. doi: 10.1016/s0092-8674(85)80025-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Gönczöl E., Andrews P. W., Plotkin S. A. Cytomegalovirus replicates in differentiated but not in undifferentiated human embryonal carcinoma cells. Science. 1984 Apr 13;224(4645):159–161. doi: 10.1126/science.6322309. [DOI] [PubMed] [Google Scholar]
- Hennighausen L., Fleckenstein B. Nuclear factor 1 interacts with five DNA elements in the promoter region of the human cytomegalovirus major immediate early gene. EMBO J. 1986 Jun;5(6):1367–1371. doi: 10.1002/j.1460-2075.1986.tb04368.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hennighausen L., Lubon H. Interaction of protein with DNA in vitro. Methods Enzymol. 1987;152:721–735. doi: 10.1016/0076-6879(87)52076-6. [DOI] [PubMed] [Google Scholar]
- LaFemina R., Hayward G. S. Constitutive and retinoic acid-inducible expression of cytomegalovirus immediate-early genes in human teratocarcinoma cells. J Virol. 1986 May;58(2):434–440. doi: 10.1128/jvi.58.2.434-440.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lenardo M. J., Staudt L., Robbins P., Kuang A., Mulligan R. C., Baltimore D. Repression of the IgH enhancer in teratocarcinoma cells associated with a novel octamer factor. Science. 1989 Jan 27;243(4890):544–546. doi: 10.1126/science.2536195. [DOI] [PubMed] [Google Scholar]
- Lubon H., Ghazal P., Hennighausen L., Reynolds-Kohler C., Lockshin C., Nelson J. Cell-specific activity of the modulator region in the human cytomegalovirus major immediate-early gene. Mol Cell Biol. 1989 Mar;9(3):1342–1345. doi: 10.1128/mcb.9.3.1342. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson J. A., Groudine M. Transcriptional regulation of the human cytomegalovirus major immediate-early gene is associated with induction of DNase I-hypersensitive sites. Mol Cell Biol. 1986 Feb;6(2):452–461. doi: 10.1128/mcb.6.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson J. A., Reynolds-Kohler C., Smith B. A. Negative and positive regulation by a short segment in the 5'-flanking region of the human cytomegalovirus major immediate-early gene. Mol Cell Biol. 1987 Nov;7(11):4125–4129. doi: 10.1128/mcb.7.11.4125. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shelbourn S. L., Sissons J. G., Sinclair J. H. Expression of oncogenic ras in human teratocarcinoma cells induces partial differentiation and permissiveness for human cytomegalovirus infection. J Gen Virol. 1989 Feb;70(Pt 2):367–374. doi: 10.1099/0022-1317-70-2-367. [DOI] [PubMed] [Google Scholar]
- Wasylyk B., Imler J. L., Chatton B., Schatz C., Wasylyk C. Negative and positive factors determine the activity of the polyoma virus enhancer alpha domain in undifferentiated and differentiated cell types. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7952–7956. doi: 10.1073/pnas.85.21.7952. [DOI] [PMC free article] [PubMed] [Google Scholar]