down-regulation; general transcription factors; repression; transcription; varicella-zoster
Abstract :
[en] Using transient transfection assays, regulation properties of varicella-zoster virus (VZV)-encoded IE63 protein were analyzed on several VZV immediate early (ORF4), early (ORF28) and late (ORF67) promoters. IE63 was shown to repress the basal activity of most of the promoters tested in epithelial (Vero) and neuronal (ND7) cells to various extents. Trans -repressing activities were also observed on heterologous viral and cellular promoters. Since a construct carrying only a TATA box sequence and a series of wild-type or mutated interleukin (IL)-8 promoters was also repressed by IE63, the role of upstream regulatory elements was ruled out. Importantly, the basal activity of a TATA-less promoter was not affected by IE63. Using a series of IE63 deletion constructs, amino acids 151-213 were shown to be essential to the transrepressing activity in Vero cells, while in ND7 cells the essential region extended to a much larger carboxy-terminal part of the protein. We also demonstrate that IE63 is capable of disrupting the transcriptional pre-initiation complex and of interacting with several general transcription factors. The central and carboxy-terminal domains of IE63 are important for these effects. Altogether, these results demonstrate that IE63 protein is a transcriptional repressor whose activity is directed towards general transcription factors.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Di Valentin, Emmanuel ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Vanderplasschen, Alain ; Université de Liège - ULiège > Département des sciences de la vie > Virologie et immunologie - GIGA-M : Coordination scientifique
Sadzot-Delvaux, Catherine ; Université de Liège - ULiège > Département des sciences de la vie > Virologie - Immunologie
Baiker, A., Bagowski, C., Ito, H., Sommer, M., Zerboni, L., Fabel, K., Hay, J., Ruyechan, W., and Arvin, A.M. (2004). The immediate-early 63 protein of varicella-zoster virus: analysis of functional domains required for replication in vitro and for T-cell and skin tropism in the SCIDhu model in vivo. J. Virol. 78, 1181-1194.
Baudoux, L., Defechereux, P., Schoonbroodt, S., Merville, M.P., Rentier, B., and Piette, J. (1995). Mutational analysis of varicella-zoster virus major immediate-early protein IE62. Nucleic Acids Res. 23, 1341-1349.
Bontems, S., Di Valentin, E., Baudoux, L., Rentier, B., Sadzot-Delvaux, C., and Piette, J. (2002). Phosphorylation of varicella-zoster virus IE63 protein by casein kinases influences its cellular localization and gene regulation activity. J. Biol. Chem. 277 21050-21060.
Buratowski, S. (1994). The basics of basal transcription by RNA polymerase II. Cell 77, 1-3.
Carrozza, M.J. and DeLuca, N.A. (1996). Interaction of the viral activator protein ICP4 with TFIID through TAF250. Mol. Cell. Biol. 16, 3085-3093.
Choy, B. and Green, M.R. (1993). Eukaryotic activators function during multiple steps of preinitiation complex assembly. Nature 366, 531-536.
Cohen, J.I., Cox, E., Pesnicak, L., Srinivas, S., and Krogmann, T. (2004). The varicella-zoster virus open reading frame 63 latency-associated protein is critical for establishment of latency. J. Virol. 78, 11833-11840.
Cohrs, R.J., Barbour, M., and Gilden, D.H. (1996). Varicella-zoster virus (VZV) transcription during latency in human ganglia: detection of transcripts mapping to genes 21, 29, 62, and 63 in a cDNA library enriched for VZV RNA. J. Virol. 70, 2789-2796.
Cohrs, R.J., Gilden, D.H., Kinchington, P.R., Grinfeld, E., and Kennedy, P.G. (2003). Varicella-zoster virus gene 66 transcription and translation in latently infected human ganglia. J. Virol. 77, 6660-6665.
Davison, A.J., and McGeoch, D.J. (1986). Evolutionary comparisons of the S segments in the genomes of herpes simplex virus type 1 and varicella-zoster virus. J. Gen. Virol. 67, 597-611.
Davison, A.J. and Scott, J.E. (1986). The complete DNA sequence of varicella-zoster virus. J. Gen. Virol. 67, 1759-1816.
Debrus, S., Sadzot-Delvaux, C., Nikkels, A.F., Piette, J., and Rentier, B. (1995). Varicella-zoster virus gene 63 encodes an immediate-early protein that is abundantly expressed during latency. J. Virol. 69, 3240-3245.
Defechereux, P., Melen, L., Baudoux, L., Merville-Louis, M.P., Rentier, B., and Piette, J. (1993). Characterization of the regulatory functions of varicella-zoster virus open reading frame 4 gene product. J. Virol. 67, 4379-4385.
Derbigny, W.A., Kim, S.K., Caughman, G.B., and O'Callaghan, D.J. (2000). The EICP22 protein of equine herpes virus 1 physically interacts with the immediate-early protein and with itself to form dimers and higher-order complexes. J. Virol. 74, 1425-1435.
Foecking, M.K. and Hofstetter, H. (1986). Powerful and versatile enhancer-promoter unit for mammalian expression vectors. Gene 45, 101-105.
Gaston, K. and Jayaraman, P.S. (2003). Transcriptional repression in eukaryotes: repressors and repression mechanisms: Cell Mol. Life Sci. 60, 721-741.
Grinfeld, E. and Kennedy, P. (2004). Translation of varicella-zoster virus genes during human ganglionic latency. Virus Genes 29, 317-319.
Grondin, B. and DeLuca, N. (2000). Herpes simplex virus type 1 ICP4 promotes transcription preinitiation complex formation by enhancing the binding of TFIID to DNA. J. Virol. 74, 11504-11510.
Gu, B., Kuddus, R., and DeLuca, N.A. (1995). Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. Mol. Cell. Biol. 15, 3618-3626.
Hahn, S. (2004). Structure and mechanism of the RNA polymerase II transcription machinery. Nat. Struct. Mol. Biol. 11, 394-403.
Hampsey, M. (1998). Molecular genetics of the RNA polymerase II general transcriptional machinery. Microbiol. Mol. Biol. Rev. 62 465-503.
Heinemeyer, T., Wingender, E., Reuter, I., Hermjakob, H., Kel, A.E., Kel, O.V., Ignatieva, E.V., Ananko, E.A., Podkolodnaya, O.A., Kolpakov, F.A., Podkolodny, N.L., and Kolchanov, N.A. (1998). Databases on transcriptional regulation: TRANSFAC, TRRD and COMPEL. Nucleic Acids Res. 26, 362-367.
Heinemeyer, T., Chen, X., Karas, H., Kel, A.E., Kel, O.V., Liebich, I., Meinhardt, T., Reuter, I., Schacherer, F., and Wingender, E. (1999). Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms. Nucleic Acids Res. 27, 318-322.
Huang, S.M. and McCance, D.J. (2002). Downregulation of the interleukin-8 promoter by human papilloma virus type 16 E6 and E7 through effects on CREB binding protein/p300 and P/CAF J. Virol. 76, 8710-8721.
Jackers, P., Defechereux, P., Baudoux, L., Lambert, C., Massaer, M., Merville-Louis, M.P., Rentier, B., and Piette, J. (1992). Characterization of regulatory functions of the varicella-zoster virus gene 63-encoded protein. J. Virol. 66, 3899-3903.
Jang, H.K., Albrecht, R.A., Buczynski, K.A., Kim, S.K., Derbigny, W.A., and O'Callaghan, D.J. (2001). Mapping the sequences that mediate interaction of the equine herpes virus 1 immediate-early protein and human TFIIB. J. Virol. 75, 10219-10230.
Kawaguchi, Y., Bruni, R., and Roizman, B. (1997). Interaction of herpes simplex virus 1 α regulatory protein ICP0 with elongation factor 1δ: ICP0 affects translational machinery. J. Virol. 71, 1019-1024.
Kennedy, P.G., Grinfeld, E., and Bell, J.E. (2000). Varicella-zoster virus gene expression in latently infected and explanted human ganglia. J. Virol. 74, 11893-11898.
Kennedy, P.G., Grinfeld, E., Bontems, S., and Sadzot-Delvaux, C. (2001). Varicella-zoster virus gene expression in latently infected rat dorsal root ganglia. Virology 289, 218-223.
Kim, S.K., Jang, H.K., Albrecht, R.A., Derbigny, W.A., Zhang, Y., and O'Callaghan, D.J. (2003). Interaction of the equine herpes virus 1 EICP0 protein with the immediate-early (IE) protein, TFIIB, and TBP may mediate the antagonism between the IE and EICP0 proteins. J. Virol. 77 2675-2685.
Kinchington, P.R., Vergnes, J.P., Defechereux, P., Piette, J., and Turse, S.E. (1994). Transcriptional mapping of the varicella-zoster virus regulatory genes encoding open reading frames 4 and 63. J. Virol. 68, 3570-3581.
Kinchington, P.R., Vergnes, J.P., and Turse, S.E. (1995). Transcriptional mapping of varicella-zoster virus regulatory proteins. Neurology 45, S33-35.
Kost, R.G., Kupinsky, H., and Straus, S.E. (1995). Varicella-zoster virus gene 63: transcript mapping and regulatory activity. Virology 209, 218-224.
Ling, P., Kinchington, P.R., Sadeghi-Zadeh, M., Ruyechan, W.T., and Hay, J. (1992). Transcription from varicella-zoster virus gene 67 (glycoprotein IV). J. Virol. 66, 3690-3698.
Lium, E.K. and Silverstein, S. (1997). Mutational analysis of the herpes simplex virus type 1 ICP0 C3HC4 zinc ring finger reveals a requirement for ICP0 in the expression of the essential alpha27 gene. J. Virol. 71, 8602-8614.
Long, M.C., Leong, V., Schaffer, P.A., Spencer, C.A., and Rice, S.A. (1999). ICP22 and the UL13 protein kinase are both required for herpes simplex virus-induced modification of the large subunit of RNA polymerase II. J. Virol. 73, 5593-5604.
Lungu, O., Panagiotidis, C.A., Annunziato, P.W., Gershon, A.A., and Silverstein, S.J. (1998). Aberrant intracellular localization of varicella-zoster virus regulatory proteins during latency. Proc. Natl. Acad. Sci. USA 95, 7080-7085.
Lynch, J.M., Kenyon, T.K., Grose, C., Hay, J., and Ruyechan, W.T. (2002). Physical and functional interaction between the varicella zoster virus IE63 and IE62 proteins. Virology 302, 71-82.
Mahalingam, R., Wellish, M., Cohrs, R., Debrus, S., Piette, J., Rentier, B., and Gilden, D.H. (1996). Expression of protein encoded by varicella-zoster virus open reading frame 63 in latently infected human ganglionic neurons. Proc. Natl. Acad. Sci. USA 93, 2122-2124.
Manet, E., Allera, C., Gruffat, H., Mikaelian, I., Rigolet, A., and Sergeant, A. (1993). The acidic activation domain of the Epstein-Barr virus transcription factor R interacts in vitro with both TBP and TFIIB and is cell-specifically potentiated by a proline-rich region. Gene Expr. 3, 49-59.
Meier, J.L., Holman, R.P., Croen, K.D., Smialek, J.E., and Straus, S.E. (1993). Varicella-zoster virus transcription in human trigeminal ganglia. Virology 193, 193-200.
Meier, J.L., Luo, X., Sawadogo, M., and Straus, S.E. (1994). The cellular transcription factor USF cooperates with varicella-zoster virus immediate-early protein 62 to symmetrically activate a bidirectional viral promoter. Mol. Cell. Biol. 14, 6896-6906.
Moon, N.S., Premdas, P., Truscott, M., Leduy, L., Berube, G., and Nepveu, A. (2001). S phase-specific proteolytic cleavage is required to activate stable DNA binding by the CDP/Cut homeodomain protein. Mol. Cell. Biol. 21, 6332-6345.
Reese, M.G., Harris, N.L., and Eeckman, F.H. (1996). Large-scale sequencing specific neural networks for promoter and splice site recognition. In: Biocomputing. Proceedings of the 1996 Pacific Symposium, L. Hunter and T.E. Klein, eds. (Singapore: World Scientific Publishing Co).
Roebuck, K.A. (1999). Regulation of interleukin-8 gene expression. J. Interferon Cytokine Res. 19, 429-438.
Sommer, M.H., Zagha, E., Serrano, O.K., Ku, C.C., Zerboni, L., Baiker, A., Santos, R., Spengler, M., Lynch, J., Grose, C., et al. (2001). Mutational analysis of the repeated open reading frames, ORFs 63 and 70 and ORFs 64 and 69, of varicella-zoster virus. J. Virol. 75, 8224-8239.
Song, C.Z., Loewenstein, P.M., Toth, K., Tang, Q., Nishikawa, A., and Green, M. (1997). The adenovirus E1A repression domain disrupts the interaction between the TATA binding protein and the TATA box in a manner reversible by TFIIB. Mol. Cell. Biol. 17, 2186-2193.
Truscott, M., Raynal, L., Premdas, P., Goulet, B., Leduy, L., Berube, G., and Nepveu, A. (2003). CDP/Cux stimulates transcription from the DNA polymerase α gene promoter. Mol. Cell. Biol. 23, 3013-3028.
Vanderplasschen, A., Markine-Goriaynoff, N., Lomonte, P., Suzuki, M., Hiraoka, N., Yeh, J.C., Bureau, F., Willems, L., Thiry, E., Fukuda, M., and Pastoret, P.P. (2000). A multipotential β-1,6-N acetylglucosaminyl-transferase is encoded by bovine herpes virus type 4. Proc. Natl. Acad. Sci. USA 97, 5756-5761.
Wood, J.N., Bevan, S.J., Coote, P.R., Dunn, P.M., Harmar, A., Hogan, P., Latchman, D.S., Morrison, C., Rougon, G., Theveniau, M., et al. (1990). Novel cell lines display properties of nociceptive sensory neurons. Proc. R. Soc. Lond. B Biol. Sci. 241, 187-194.
Yamamoto, S., Watanabe, Y., van der Spek, P.J., Watanabe, T., Fujimoto, H., Hanaoka, F., and Ohkuma, Y. (2001). Studies of nematode TFIIE function reveal a link between Ser-5 phosphorylation of RNA polymerase II and the transition from transcription initiation to elongation. Mol. Cell. Biol. 21, 1-15.