Summary
Truncated α 4 genes were introduced into BHK tk− cells along with the neomycin phosphotransferase gene, that confers resistance to the eukaryotic antibiotic G 418, driven by the HSV-1 β tk promoter (β tk−neor). Stably transformed cell lines were obtained and studied for the ability of the resident truncated α 4 genes to regulate the expression of the β tk−neor, and for the ability of the truncated α 4 polypeptides to localize to the nuclei of transformed cells. The results indicated that the domain(s) for β gene induction and for nuclear localization of the α 4 protein are located within the N-terminal 288 amino acids of the protein.
References
Ackermann M, Braun D, Pereira L, Roizman B (1984) Characterization of herpes simplex virus 1 α proteins 0, 4, and 27 with monoclonal antibodies. J Virol 52: 108–118
Arsenakis M, Hubenthal-Voss J, Campadelli-Fiume G, Pereira L, Roizman B (1986) Construction and properties of a cell line constitutively expressing the herpes simplex virus glycoprotein B dependent on functional α 4 protein. J Virol 60: 674–682
Arsenakis M, Campadelli-Fiume G, Roizman B (1988) Regulation of glycoprotein D synthesis: does α 4, the major regulatory protein of herpes simplex virus 1, regulate late genes both positively and negatively? J Virol 62: 148–158
DeLuca NA, Schaffer PA (1988) Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP 4. J Virol 62: 732–743
Dixon RAF, Schaffer PA (1980) Fine-structure mapping and functional analysis of temperature-sensitive mutants in the gene encoding the herpes simplex virus type 1 immediate early protein VP 175. J Virol 36: 189–203
Faber SW, Wilcox KW (1986) Association of the HSV-1 regulatory protein ICP 4 with specific nucleotide sequences in DNA. Nucleic Acids Res 14: 6067–6082
Honess RW, Roizman B (1974) Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral protein. J Virol 14: 8–19
Honess RW, Roizman B (1975) Regulation of herpes simplex macromolecular synthesis requires functional viral polypeptides. Proc Natl Acad Sci USA 72: 1276–1280
Hubenthal-Voss J, Houghten RA, Pereira L, Roizman B (1988) Mapping of functional and antigenic domains of the α 4 protein of herpes simplex virus 1. J Virol 62: 454–462
Imbalzano AN, Shepard AA, DeLuca NA (1990) Functional relevance of specific interactions between herpes simplex virus type 1 ICP 4 and sequences from the promoter-regulatory domain of the viral thymidine kinase gene. J Virol 64: 2620–2631
Kalderon D, Roberts B, Richardson WD, Smith AE (1984) Sequence requirements for nuclear localization of SV 40 large T antigen. Nature 311: 33–38
Knipe DM, Senechek D, Rice SA, Smith JL (1987) Stage in the nuclear association of the herpes simplex virus transcriptional activator protein ICP 4. J Virol 61: 274–284
Kristie TM, Roizman B (1986) α 4, the major regulatory protein of herpes simplex virus type 1, is stably and specifically associated with the promoter-regulatory domains of α genes and selected other viral genes. Proc Natl Acad Sci USA 83: 3218–3222
Kristie TM, Roizman B (1986) DNA-binding site of major regulatory protein α 4 specifically associated with promoter-regulatory domains of α genes of herpes simplex virus type 1. Proc Natl Acad Sci USA 83: 4700–4704
Mackem S, Roizman B (1981) Regulation of herpesvirus macromolecular synthesis: temporal order of transcription of α genes is not dependent on the stringency of inhibition of protein synthesis. J Virol 40: 319–320
Mavromara-Nazos P, Silver S, Hubenthal-Voss J, McKnight JLC, Roizman B (1986) Regulation of herpes simplex virus 1 genes: α gene sequence requirements for transient induction of indicator genes regulated by β or late (γ2) promoters. Virology 149: 152–164
McGeoch DJ, Dolan A, Donald S, Brauer DHK (1986) Complete DNA sequence of the short repeat region in the genome of herpes simplex virus. Nucleic Acids Res 14: 1727–1745
Michael N, Spector D, Mavromara-Nazos P, Kristie TM, Roizman B (1988) The DNA binding properties of the major regulatory protein α 4 of herpes simplex virus. Science 239: 1531–1534
Muller MT (1987) Binding of the herpes simplex virus type 1 gene product ICP 4 to its own transcription start site. J Virol 61: 858–865
Post LE, Mackem S, Roizman B (1981) The regulation of α genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with α gene promoters. Cell 24: 555–565
Preston VG (1981) Fine-structure mapping of herpes simplex virus type 1 temperature-sensitive mutations within the short repeat region of the genome. J Virol 39: 150–161
Randall RE, Dinwoodie N (1986) Intracellular localization of herpes simplex virus immediate-early and delayed-early proteins: evidence that ICP 4 is associated with progeny virus DNA. J Gen Virol 67: 2163–2177
Richardson WD, Roberts BC, Smith AE (1986) Nuclear localization signals in polyoma virus large T. Cell 44: 77–85
Roizman B, Kozak M, Honess RW, Hayward GS (1974) Regulation of herpes virus macromolecular synthesis: evidence for multivalent regulation of herpes simplex 1 RNA and protein synthesis. Cold Spring Harbor Symp Quant Biol 39: 687–701
Shepard AA, Imbalzano AN, DeLuca NA (1989) Separation of primary structural components conferring autoregulation, transactivation, and DNA-binding properties to the herpes simplex virus transcriptional regulatory protein ICP 4. J Virol 63: 3714–3728
Shepard AA, DeLuca NA (1989) Intragenic complementation among partial peptides of herpes simplex virus regulatory protein ICP 4. J Virol 63: 1203–1211
Smiley JR, Johnson DC, Pizer LI, Everett RD (1992) The ICP 4 binding sites in the herpes simplex virus type 1 glycoprotein D (gD) promoter are not essential for efficient gD transcription during virus infection. J Virol 66: 623–631
Southern PJ, Berg P (1982) Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV 40 early region promoter. J Mol Appl Genet 1: 327–341
Tedder DG, Everett RD, Wilkox KW, Beard P, Pizer LI (1989) ICP 4 binding sites in the promoter and coding regions of the herpes simplex virus gD gene contribute to activation of in vitro transcription by ICP 4. J Virol 63: 2510–2520
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sivropoulou, A., Arsenakis, M. Mapping of the functional domains of the α 4 protein of herpes simplex virus 1. Archives of Virology 129, 317–325 (1993). https://doi.org/10.1007/BF01316907
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01316907