Abstract
The herpes simplex virus DNA genome consists of two covalently linked components, L and S. The unique sequences of the L component are flanked by 9-kilobase-pair inverted repeat sequences ab and b'a', whereas those of the S component are flanked by 6.5-kilobase-pair inverted repeat sequences c'a' and ca. We report that the 500-base-pair a sequence contains the promoter-regulatory domain and the transcription initiation site of a diploid gene, the coding sequences of which are located in the b sequences of the inverted repeats of the L component. The chimeric gene constructed by fusion of the a sequence to the coding sequences of the thymidine kinase gene and recombined into the viral genome was regulated as a gamma 1 gene. The size of the protein predicted from its sequence is 358 amino acids; it was designated as infected cell protein (ICP) 34.5. Thus, the inverted repeats flanking the unique sequences of the L component contain two genes specifying ICP0 and ICP34.5, respectively. Moreover, in addition to the cis-acting sites for the inversion of L and S components relative to each other, for cleavage of unit length DNA molecules from head-to-tail concatemers, and for packaging of the DNA into capsids, the a sequence also contains the promoter-regulatory domain and transcription initiation sites of a gene.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Batterson W., Roizman B. Characterization of the herpes simplex virion-associated factor responsible for the induction of alpha genes. J Virol. 1983 May;46(2):371–377. doi: 10.1128/jvi.46.2.371-377.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berget S. M. Are U4 small nuclear ribonucleoproteins involved in polyadenylation? Nature. 1984 May 10;309(5964):179–182. doi: 10.1038/309179a0. [DOI] [PubMed] [Google Scholar]
- Broach J. R., Guarascio V. R., Jayaram M. Recombination within the yeast plasmid 2mu circle is site-specific. Cell. 1982 May;29(1):227–234. doi: 10.1016/0092-8674(82)90107-6. [DOI] [PubMed] [Google Scholar]
- Bukhari A. I., Ambrosio L. The invertible segment of bacteriophage Mu DNA determines the adsorption properties of Mu particles. Nature. 1978 Feb 9;271(5645):575–577. doi: 10.1038/271575a0. [DOI] [PubMed] [Google Scholar]
- Campbell M. E., Palfreyman J. W., Preston C. M. Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J Mol Biol. 1984 Nov 25;180(1):1–19. doi: 10.1016/0022-2836(84)90427-3. [DOI] [PubMed] [Google Scholar]
- Chou J., Roizman B. Isomerization of herpes simplex virus 1 genome: identification of the cis-acting and recombination sites within the domain of the a sequence. Cell. 1985 Jul;41(3):803–811. doi: 10.1016/s0092-8674(85)80061-1. [DOI] [PubMed] [Google Scholar]
- Conley A. J., Knipe D. M., Jones P. C., Roizman B. Molecular genetics of herpes simplex virus. VII. Characterization of a temperature-sensitive mutant produced by in vitro mutagenesis and defective in DNA synthesis and accumulation of gamma polypeptides. J Virol. 1981 Jan;37(1):191–206. doi: 10.1128/jvi.37.1.191-206.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davison A. J., Wilkie N. M. Nucleotide sequences of the joint between the L and S segments of herpes simplex virus types 1 and 2. J Gen Virol. 1981 Aug;55(Pt 2):315–331. doi: 10.1099/0022-1317-55-2-315. [DOI] [PubMed] [Google Scholar]
- Ejercito P. M., Kieff E. D., Roizman B. Characterization of herpes simplex virus strains differing in their effects on social behaviour of infected cells. J Gen Virol. 1968 May;2(3):357–364. doi: 10.1099/0022-1317-2-3-357. [DOI] [PubMed] [Google Scholar]
- Hayward G. S., Jacob R. J., Wadsworth S. C., Roizman B. Anatomy of herpes simplex virus DNA: evidence for four populations of molecules that differ in the relative orientations of their long and short components. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4243–4247. doi: 10.1073/pnas.72.11.4243. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis. I. Cascade regulation of the synthesis of three groups of viral proteins. J Virol. 1974 Jul;14(1):8–19. doi: 10.1128/jvi.14.1.8-19.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Honess R. W., Roizman B. Regulation of herpesvirus macromolecular synthesis: sequential transition of polypeptide synthesis requires functional viral polypeptides. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1276–1280. doi: 10.1073/pnas.72.4.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jenkins F. J., Howett M. K. Characterization of mRNAs that map in the BglII N fragment of the herpes simplex virus type 2 genome. J Virol. 1984 Oct;52(1):99–107. doi: 10.1128/jvi.52.1.99-107.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kieff E. D., Bachenheimer S. L., Roizman B. Size, composition, and structure of the deoxyribonucleic acid of herpes simplex virus subtypes 1 and 2. J Virol. 1971 Aug;8(2):125–132. doi: 10.1128/jvi.8.2.125-132.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kristie T. M., Roizman B. Separation of sequences defining basal expression from those conferring alpha gene recognition within the regulatory domains of herpes simplex virus 1 alpha genes. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4065–4069. doi: 10.1073/pnas.81.13.4065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Locker H., Frenkel N. BamI, KpnI, and SalI restriction enzyme maps of the DNAs of herpes simplex virus strains Justin and F: occurrence of heterogeneities in defined regions of the viral DNA. J Virol. 1979 Nov;32(2):429–441. doi: 10.1128/jvi.32.2.429-441.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Differentiation between alpha promoter and regulator regions of herpes simplex virus 1: the functional domains and sequence of a movable alpha regulator. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4917–4921. doi: 10.1073/pnas.79.16.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: the alpha 27 gene promoter-thymidine kinase chimera is positively regulated in converted L cells. J Virol. 1982 Sep;43(3):1015–1023. doi: 10.1128/jvi.43.3.1015-1023.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackem S., Roizman B. Structural features of the herpes simplex virus alpha gene 4, 0, and 27 promoter-regulatory sequences which confer alpha regulation on chimeric thymidine kinase genes. J Virol. 1982 Dec;44(3):939–949. doi: 10.1128/jvi.44.3.939-949.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- McKnight S. L. The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Res. 1980 Dec 20;8(24):5949–5964. doi: 10.1093/nar/8.24.5949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mizuuchi K., Weisberg R., Enquist L., Mizuuchi M., Buraczynska M., Foeller C., Hsu P. L., Ross W., Landy A. Structure and function of the phage lambda att site: size, int-binding sites, and location of the crossover point. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 1):429–437. doi: 10.1101/sqb.1981.045.01.057. [DOI] [PubMed] [Google Scholar]
- Mocarski E. S., Deiss L. P., Frenkel N. Nucleotide sequence and structural features of a novel US-a junction present in a defective herpes simplex virus genome. J Virol. 1985 Jul;55(1):140–146. doi: 10.1128/jvi.55.1.140-146.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mocarski E. S., Post L. E., Roizman B. Molecular engineering of the herpes simplex virus genome: insertion of a second L-S junction into the genome causes additional genome inversions. Cell. 1980 Nov;22(1 Pt 1):243–255. doi: 10.1016/0092-8674(80)90172-5. [DOI] [PubMed] [Google Scholar]
- Mocarski E. S., Roizman B. Site-specific inversion sequence of the herpes simplex virus genome: domain and structural features. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7047–7051. doi: 10.1073/pnas.78.11.7047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mocarski E. S., Roizman B. Structure and role of the herpes simplex virus DNA termini in inversion, circularization and generation of virion DNA. Cell. 1982 Nov;31(1):89–97. doi: 10.1016/0092-8674(82)90408-1. [DOI] [PubMed] [Google Scholar]
- Nash H. A. Integration and excision of bacteriophage lambda. Curr Top Microbiol Immunol. 1977;78:171–199. doi: 10.1007/978-3-642-66800-5_6. [DOI] [PubMed] [Google Scholar]
- Pellett P. E., McKnight J. L., Jenkins F. J., Roizman B. Nucleotide sequence and predicted amino acid sequence of a protein encoded in a small herpes simplex virus DNA fragment capable of trans-inducing alpha genes. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5870–5874. doi: 10.1073/pnas.82.17.5870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Post L. E., Mackem S., Roizman B. Regulation of alpha genes of herpes simplex virus: expression of chimeric genes produced by fusion of thymidine kinase with alpha gene promoters. Cell. 1981 May;24(2):555–565. doi: 10.1016/0092-8674(81)90346-9. [DOI] [PubMed] [Google Scholar]
- Sheldrick P., Berthelot N. Inverted repetitions in the chromosome of herpes simplex virus. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 2):667–678. doi: 10.1101/sqb.1974.039.01.080. [DOI] [PubMed] [Google Scholar]
- Silver S., Roizman B. gamma 2-Thymidine kinase chimeras are identically transcribed but regulated a gamma 2 genes in herpes simplex virus genomes and as beta genes in cell genomes. Mol Cell Biol. 1985 Mar;5(3):518–528. doi: 10.1128/mcb.5.3.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smiley J. R., Fong B. S., Leung W. C. Construction of a double-jointed herpes simplex viral DNA molecule: inverted repeats are required for segment inversion, and direct repeats promote deletions. Virology. 1981 Aug;113(1):345–362. doi: 10.1016/0042-6822(81)90161-6. [DOI] [PubMed] [Google Scholar]
- Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
- Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
- Vlazny D. A., Kwong A., Frenkel N. Site-specific cleavage/packaging of herpes simplex virus DNA and the selective maturation of nucleocapsids containing full-length viral DNA. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1423–1427. doi: 10.1073/pnas.79.5.1423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wadsworth S., Jacob R. J., Roizman B. Anatomy of herpes simplex virus DNA. II. Size, composition, and arrangement of inverted terminal repetitions. J Virol. 1975 Jun;15(6):1487–1497. doi: 10.1128/jvi.15.6.1487-1497.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wagner M. J., Summers W. C. Structure of the joint region and the termini of the DNA of herpes simplex virus type 1. J Virol. 1978 Aug;27(2):374–387. doi: 10.1128/jvi.27.2.374-387.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zieg J., Silverman M., Hilmen M., Simon M. Recombinational switch for gene expression. Science. 1977 Apr 8;196(4286):170–172. doi: 10.1126/science.322276. [DOI] [PubMed] [Google Scholar]
- Zieg J., Simon M. Analysis of the nucleotide sequence of an invertible controlling element. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4196–4200. doi: 10.1073/pnas.77.7.4196. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van de Putte P., Cramer S., Giphart-Gassler M. Invertible DNA determines host specificity of bacteriophage mu. Nature. 1980 Jul 17;286(5770):218–222. doi: 10.1038/286218a0. [DOI] [PubMed] [Google Scholar]