The right end of the unique region of the genome of human herpesvirus 6 U1102 contains a candidate immediate early gene enhancer and a homologue of the human cytomegalovirus US22 gene family
The nucleotide sequence of a 12 kbp HindIII fragment (HindIII C) from the right end of the unique component of the genome of human herpesvirus 6 (HHV-6) (strain U1102) was determined. The sequence has a mean G+C content of 42% and contains approximately 28 copies of a tandemly repeated 104 to 107 bp element, which, with a single exception, contain a cleavage site for KpnI (the KpnI repeats). Each of these elements contains potential binding sites for transcription factors NF-κB and AP2. The KpnI repeats lie immediately upstream of a region previously identified as a candidate immediate early (IE) gene locus and therefore may constitute an IE gene enhancer element. One incomplete and six complete open reading frames (ORFs) were identified in the unique sequence of the HindIII C fragment. The predicted products of these ORFs do not include homologues of proteins encoded by members of the alpha- or gammaherpesvirus subfamily. However, the HindIII C fragment does contain a homologue of the US22 gene family, previously found only in the betaherpesvirus human cytomegalovirus (HCMV). These findings provide evidence that the close phylogenetic relationship between HHV-6 and HCMV is not confined to the betaherpesvirus-specific arrangement of conserved replicative and structural genes which has been demonstrated previously.
AkriggA.,
WilkinsonG. W. G.,
OramJ. D.1985; The structure of the major immediate early gene of human cytomegalovirus strain AD169. Virus Research 2:107–121
BankierA. T.,
WestonK.,
BarrellB. G.1988; Random cloning and sequencing by the M13/dideoxynucleotide chain termination method. Methods in Enzymology 155:51–93
BoshartM.,
WeberF.,
JahnG.,
Dorsch-HäslerK.,
Flecken-steinB.,
SchaffnerW.1985; A very strong enhancer is located upstream of an immediate early gene of human cytomegalovirus. Cell 41:521–530
CarriganD. R.,
KnoxK. K.,
RusslerM. A.1990; Suppression of human immunodeficiency virus type 1 replication by human herpesvirus-6. Journal of Infectious Diseases 162:844–851
ChangY.-N.,
CrawfordS.,
StallJ.,
RawlinsD. R.,
JeangK.-T.,
HaywardG. S.1990; The palindromic series I repeats in the simian cytomegalovirus major immediate-early promoter behave as both strong basal enhancers and cyclic AMP response elements. Journal of Virology 64:264–277
CheeM. S.,
BankierA. T.,
BeckS.,
BohniR.,
BrownC. M.,
CernyR.,
HorsnellT.,
HutchisonC. A.III,
KouzaridesT.,
MartignettiJ. A.,
PreddieE.,
SatchwellS. C.,
TomlinsonP.,
WestonK. M.,
BarrellB. G.1990; Analysis of the protein coding content of the sequence of human cytomegalovirus strain AD 169. Current Topics in Microbiology and Immunology 154:125–169
Dorsch-HaslerK.,
KeilG. M.,
WeberF.,
JasinM.,
SchaffnerW.,
KoszinowskiU. H.1985; A long and complex enhancer activates transcription of the gene coding for the highly abundant immediate early mRNA in murine cytomegalovirus. Proceedings of the National Academy of Sciences, U.S.A. 82:8325–8329
DowningR. G.,
SewankamboN.,
SerwaddaD.,
HonessR.,
CrawfordD.,
JarrettR.,
GriffinB. E.1987; Isolation of human lymphotropic herpesviruses from Uganda. Lancet ii 390
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
FickenscherH.,
StammingerT.,
RügerR.,
FleckensteinB.1989; The role of a repetitive palindromic sequence element in the human cytomegalovirus immediate early enhancer. Journal of General Virology 70:107–123
FlemingtonE.,
SpeckS. H.1990; Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1. Journal of Virology 64:1217–1226
GlassC. K.,
HollowayJ. M.,
DevaryO. V.,
RosenfeldM. G.1988; The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen response elements. Cell 54:313–323
HonessR. W.,
CompelsU. A.,
BarrellB. G.,
CraxtonM.,
CameronK. R.,
StadenR.,
ChangY.-N.,
HaywardG. S.1989; Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes. Journal of General Virology 70:837–855
HunninghakeG. W.,
MonickM. M.,
LiuB.,
StinskiM. F.1989; The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements. Journal of Virology 63:3026–3033
ImagawaM.,
ChiuR.,
KarinM.1987; Transcription factor AP-2 mediates induction by two different signal-transduction pathways: protein kinase C and cAMP. Cell 51:251–260
JeangK. T.,
HaywardS. D.1983; Organization of the Epstein-Barr virus DNA molecule III. Location of the P3HR1 deletion junction and characterization of the Not I repeat units that form part of the template for an abundant 12-O-tetradecanoylphorbol-13-acetate-induced mRNA transcript. Journal of Virology 48:135–148
JeangK. T.,
RawlinsD. R.,
RosenfeldP.,
SheroJ. H.,
KellyT.,
HaywardG. S.1987; Multiple tandemly repeated binding sites for cellular nuclear factor 1 that surround the major immediate early promoters of simian and human cytomegalovirus. Journal of Virology 61:1559–1570
JonesN. C.,
RigbyP. W.,
ZiffE. B.1988; Trara acting protein factors and the regulation of eukaryotic transcription lessons from studies on DNA tumor viruses. Genes and Development 2:267–281
KnowlesW. A.,
GardnerS. D.1988; High prevalence of antibody to human herpesvirus-6 and seroconversion associated with rash in two infants. Lancet ii:912–913
KondoK.,
KondoT.,
OkunoT.,
TakahashiM.,
YamanishiK.1991; Latent human herpesvirus 6 infection of human monocytes/ macrophages. Journal of General Virology 72:1401–1408
KouzaridesT.,
BankierA. T.,
SatchwellS. C.,
PreddieE.,
BarrellB. G.1988; An immediate early gene of human cytomegalovirus encodes a membrane glycoprotein. Virology 165:151–164
LauxG.,
FreeseK. U.,
BornkammG. W.1985; Structure and evolution of two related transcription units of Epstein-Barr virus carrying small tandem repeats. Journal of Virology 56:987–995
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
LevyJ. A.,
GreenspanD.,
FerroF.,
LennetteE. T.1990; Frequent isolation of HHV-6 from saliva and seroprevalence of the virus in the population. Lancet i:1047–1050
LopezC.,
PellettP. E.,
StewartJ.,
GoldsmithC.,
SanderlinK.,
BlackJ.,
WarfieldD.,
FeorinoP.1988; Characteristics of human herpesvirus-6. Journal of Infectious Diseases 157:1271–1273
LubonH.,
GhazalP.,
HennighausenL.,
Reynolds-KohlerC.,
LockshinC.,
NelsonJ. A.1989; Cell-specific activity of the modulator region in the human cytomegalovirus major immediate early gene. Molecular and Cellular Biology 9:1342–1345
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.,
DolanA.,
DonaldS.,
BrauerD. H. K.1986; Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Research 14:1727–1745
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
McLauchlanJ.,
GaffneyD.,
WhittonJ. L.,
ClementsJ. B.1985; The consensus sequence YGTGTTYY located downstream of the AATAAA signal is required for efficient formation of mRNA 3′ termini. Nucleic Acids Research 13:1347–1368
MartinM. E. D.,
NicholasJ.,
ThomsonB. J.,
NewmanC.,
HonessR. W.1991a; Identification of a transactivating function mapping to the putative immediate early locus of human herpesvirus-6. Journal of Virology 65:5381–5390
MartinM. E. D.,
ThomsonB. J.,
HonessR. W.,
CraxtonM. A.,
CompelsU. A.,
LiuU. A.,
LittlerE.,
ArrandJ. R.,
TeoI.,
JonesM. D.1991b; The genome of human herpesvirus 6: maps of unit-length and concatemeric genomes for nine restriction endonucleases. Journal of General Virology 72:157–168
MocarskiE. S.,
PereiraL.,
McCormickA. L.1988; Human cytomegalovirus ICP22, the product of the HWLF1 reading frame, is an early nuclear protein that is released from cells. Journal of General Virology 69:2613–2621
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
NelsonJ. A.,
GroudineM.1986; Transcriptional regulation of the human cytomegalovirus major immediate-early gene is associated with induction of DNase I-hypersensitive sites. Molecular and Cellular Biology 6:452–461
NelsonJ. A.,
Reynolds-KohlerC.,
SmithB. A.1987; Negative and positive regulation by a short segment in the 5′ flanking region of the human cytomegalovirus major immediate-early gene. Molecular and Cellular Biology 7:4125–4129
OkunoT.,
TakahashiK.,
BalachandraK.,
ShirakiK.,
YamanishiK.,
TakahashiM.,
BabaK.1989; Seroepidemi-ology of human herpesvirus 6 infection in normal children and adults. Journal of Clinical Microbiology 27:651–653
RusslerS. K.,
TapperM. A.,
KnoxK. K.,
LiepensA.,
CarriganD. R.1991; Pneumonitis associated with coinfection by human herpesvirus 6 and legionalla in an immunocompetent adult. American Journal of Pathology 138:1405–1411
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 234:596–600
SangerF.,
NicklenS.,
CoulsonA. R.1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A. 74:5463–5467
StadenR.1982; Automation of the computer handling of the gel reading data produced by the shotgun method of DNA sequencing. Nucleic Acids Research 10:4731–4751
StadenR.1984; Measurement of the effects that coding for a protein has on a DNA sequence and their use for finding genes. Nucleic Acids Research 12:551–567
StinksiM. F.,
RoehrT. J.1985; Activation of the major immediate early gene of human cytomegalovirus by cis-acting elements in the promoter-regulatory sequence and virus-specific rram-acting components. Journal of Virology 55:431–441
ThomsenD. R.,
StenbergR. M.,
GoinsW. F.,
StinskiM. F.1984; Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. Proceedings of the National Academy of Sciences, U.S.A. 81:659–663
ThomsonB. J.,
EfstathiouS.,
HonessR. W.1991a; Acquisition of the human adeno-associated virus type-2 rep gene by human herpesvirus-6. Nature, London 351:78–80
WardK. N.,
GrayJ. J.,
EfstathiouS.1989; Brief report: primary human herpesvirus 6 infection in a patient following liver transplantation from a seropositive donor. Journal of Medical Virology 28:69–72
WestonK.,
BarrellB. G.1986; Sequence of the short unique region, short repeats and part of the the long repeat of human cytomegalovirus. Journal of Molecular Biology 192:177–208
YamanishiK.,
OkunoT.,
ShirakiK.,
TakahashiM.,
KondoT.,
AsanoY.,
KurataT.1988; Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lanceti1065–1067
The right end of the unique region of the genome of human herpesvirus 6 U1102 contains a candidate immediate early gene enhancer and a homologue of the human cytomegalovirus US22 gene family