Uracil-DNA glycosylase encoded in many species functions as a DNA repair enzyme that removes uracil residues from DNA. To investigate the potential function of uracil-DNA glycosylase encoded by human herpesvirus 6 (HHV-6), we sequenced a DNA clone (pSTY09), identified an open reading frame of 765 bp and compared the putative amino acid sequence with other uracil-DNA glycosylases, by computer analysis. The amino acid sequence of HHV-6 had similarities to other uracil-DNA glycosylases, with the highest degree of similarity to those of human cytomegalovirus and Epstein-Barr virus. Two strongly conserved regions in uracil-DNA glycosylase of other species also existed in HHV-6. The gene product which was expressed in Escherichia coli demonstrated uracil-DNA glycosylase activity. This is the first report to identify and characterize the uracil-DNA glycosylase gene in HHV-6.
AmannE., OchsB., AbelK. J.1988; Tightly regulated tac promoter vectors useful for the expression of unfused and fused proteins in Escherichia coli. Gene 69:301–315
AubinJ., CollandreH., CandottiD., IngrandD., RouziouxC., BurgardM., RichardS., HurauxJ., AgutH.1991; Several groups among human herpesvirus 6 strains can be distinguished by Southern blotting and polymerase chain reaction. Journal of Clinical Microbiology 29:367–372
AubinJ. -T., AgutH., CollandreH., YamanishiK., ChandranB., MontagnierL., HurauxJ. -M.1993; Antigenic and genetic differentiation of the two putative types of human herpesvirus 6. Journal of Virological Methods 41:223–234
CaradonnaS., ChengY. -C.1980; Uracil-DNA glycosylase: purification and properties of this enzyme isolated from blast cells of acute myelocytic leukemia patients. Journal of Biological Chemistry 255:2293–2300
CaradonnaS., WorradD., LiretteR.1987; Isolation of a herpes simplex virus cDNA encoding the DNA repair enzyme uracil-DNA glycosylase. Journal of Virology 61:3040–3047
ChandranB., TirawatnapongS., PfeifferB., AblashiD. V.1992; Antigenic relationships among human herpesvirus-6 isolations. Journal of Medical Virology 37:247–254
CheeM. S., BankierA. T., BeckS., BohniR., BrownC. M., CernyR., HorsnellT., HutchisonC. A.IIIKouzaridesT., MartignettiJ. A., PreddieE., SatchwellS. C., TomlinsonP., WestonK. M., BarrellB. G.1990; Analysis of the protein coding content of the sequence of human cytomegalovirus strain AD169. Current Topics in Microbiology and Immunology 154:125–169
EfstathiouS., LawrenceG. L., BrownC. M., BarrellB. G.1992; Identification of homologues to the human cytomegalovirus US22 gene family in human herpesvirus 6. Journal of General Virology 73:1661–1671
FocherF., MazzarelloP., VerriA., HubscherU., SpadariS.1990; Activity profiles of enzymes that control the uracil incorporation into DNA during neuronal development. Mutation Research 237:65–73
GompelsU. A., CarriganD. C., CarssA. L., ArnoJ.1993; Two groups of human herpesvirus 6 identified by sequence analysis of laboratory strains and variants from Hodgkin’s lymphoma and bone marrow transplant patients. Journal of General Virology 74:613–622
JosephsS. F., SalahuddinS. Z., AblashiD. V., SchachterF., Wong-StaalF., GalloR. C.1986; Genomic analyses of the human B lymphotropic virus. Science 234:601–603
JosephsS. F., AblashiD. V., SalahuddinS. Z., JagodzinskiL. L., Wong-StaalF., GalloR. C.1992; Identification of the human herpesvirus 6 glycoprotein H and putative long tegument protein genes. Journal of Virology 65:5597–5604
KondoK., KondoT., OkunoT., TakahashiM., YamanishiK.1991; Latent human herpesvirus 6 infection of human monocytes/ macrophages. Journal of General Virology 72:1401–1408
KondoK., NagafujiH., HataA., TomomoriC., YamanisiK.1993; Association of human herpesvirus 6 infection of the central nervous system with recurrence of febrile convulsions. Journal of Infectious Diseases 167:1197–1200
KunkelT. A., RobertsJ. D., ZakourR. A.1987; Rapid and efficient site-specific mutagenesis without phenotypic selection. Methods in Enzymology 154:367–382
LawrenceG. L., CheeM., CraxtonM. A., GompelsU. A., HonessR. W., BarrellB. G.1990; Human herpesvirus 6 is closely related to human cytomegalovirus. Journal of Virology 64:287–299
LindahlT.1974; An N-glycosidase from Escherichia coli that releases free uracil from DNA containing deaminated cytosine residues. Proceedings of the National Academy of Sciences, U.S.A 71:3649–3653
LiuD. X., GompelsU. A., NicholasJ., LelliottC.1993; Identification and expression of the human herpesvirus 6 glycoprotein H and interaction with an accessory 40K glycoprotein. Journal of General Virology 74:1847–1857
LussoP., MarkhamP. D., TschachlerE., Di Marco VeroneseF., SalahuddinS. Z., AblashiD. V., PahwaS., GrohnK., GalloR. C.1988; In vitro cellular tropism of human B-lympho- tropic virus (human herpesvirus-6). Journal of Experimental Medicine 167:1659–1670
McGeochD. J., DalrympleM. A., DavisonA. J., DolanA., FrameM. C., McNabD., PerryL. J., ScottJ. E., TaylorP.1988; the complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:1531–1574
McGeochD. J., CunninghamC., McIntyreG., DolanA.1991; Comparative sequence analysis of the long repeat regions and adjoining parts of the long unique regions in the genomes of herpes simplex viruses types 1 and 2. Journal of General Virology 72:3057–3075
MartinJ. H., DohnerD. E., WellinghoffW. J., GelbL. D.1982; Restriction endonuclease analysis of varicella-zoster vaccine virus and wild type DNAs. Journal of Medical Virology 9:69–76
MullaneyJ., MossH. W.McLMcGeochD. J.1989; Gene UL2 of herpes simplex virus type 1 encodes a uracil-DNA glycosylase. Journal of General Virology 70:449–454
NeipelF., EllingerK., FleckensteinB.1991; The unique region of the human herpesvirus 6 genome is essentially collinear with the UL segment of human cytomegalovirus. Journal of General Virology 72:2293–2297
OlsenL. C., AaslandR., WittwerC. U., KrokenH. E., HellandD. E.1989; Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme. EMBO Journal 8:3121–3125
PercivalK. J., KleinM. B., BurgersP. M. J.1989; Molecular cloning and primary structure of uracil-DNA-glycosylase gene from Saccharomyces cerevisiae. Journal of Biological Chemistry 264:2593–2598
PerryL. J., McGeochD. J.1988; The DNA sequences of the long repeat region and adjoining parts of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69:2831–2846
SalahuddinS. Z., AblashiD. V., MarkhamP. D., JosephsS. F., SturzeneggerS., KaplanM., HalliganG., BiberfeldP., Wong-StaalF., KramarskyB., GalloR. C.1986; Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders. Science 234:596–601
SangerF., NicklenS., CoulsonA. R.1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A 74:5463–5467
SchirmerE. C., WyattL. S., YamanishiK., RodriguezW. J., FrenkelN.1991; Differentiation between two distinct classes of viruses now classified as human herpesvirus 6. Proceedings of the National Academy of Sciences, U.S.A 88:5966–5926
VarshneyU., HutcheonT., Van De SandeJ. 1988; Sequence analysis, expression, and conservation of Escherichia coli uracil- DNA glycosylase and its gene (ung). Journal of Biological Chemistry 263:7776–7784
WangZ., MosbaughD. W.1988; Uracil-DNA glycosylase inhibition of bacteriophage PBS2: cloning and effects of expression of the inhibitor gene in Escherichia coli. Journal of Bacteriology 170:1082–1091
WilliamsM. V., AblashiD. V., SalahuddinS. Z., GlaserR.1989; Demonstration of the human herpesvirus 6-induced DNA polymerase and DNase. Virology 173:223–230
WintersT. A., WilliamsM. V.1990; Use of the PBS2 uracil-DNA glycosylase inhibitor to differentiate the uracil-DNA glycosylase activities encoded by herpes simplex virus type 1 and 2. Journal of Virological Methods 29:233–242
WyattL. S., BalachandranN., FrenkelN.1990; Variations in the replication and antigenic properties of human herpesvirus 6 strains. Journal of Infectious Diseases 162:852–857
YamamotoT., MukaiT., KondoK., YamanishiK.1994; Variation of DNA sequence in immediate-early gene of human herpesvirus 6 and variant identification by PCR. Journal of Clinical Microbiology 32:473–476
YamanishiK., OkunoT., ShirakiK., TakahashiM., KondoT., AsanoY., KurataT.1988; Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet i:1065–1067