Human herpesvirus-8 (HHV-8) is a γ2 lymphotropic herpesvirus associated with Kaposi’s sarcoma, a major neoplasm of AIDS patients, and with other AIDS-related neoplasms. The HHV-8 ORF 57 gene is conserved throughout the herpesvirus family and has a herpes simplex virus type 1 homologue, IE63 (also termed ICP27), which is an essential regulatory protein and acts at both transcriptional and post-transcriptional levels. We show that, contrary to the published HHV-8 sequence, which predicts a protein of 275 amino acids, the ORF 57 gene is spliced, contains a single intron and encodes a protein of 455 amino acids. For several gammaherpesviruses examined, the upstream coding exon is 16–17 amino acids in length and is rich in methionine residues. When ORF 57 was fused to the gene for enhanced green fluorescent protein (EGFP), the fusion protein exhibited a punctate nuclear distribution that co-localized with the cellular splicing factor SC-35. Unlike the IE63–EGFP fusion protein, ORF 57–EGFP did not shuttle from the nucleus to the cytoplasm in the presence of actinomycin D. However, ORF 57–EGFP was capable of shuttling from a transfected monkey nucleus to a recipient mouse nucleus in an interspecies heterokaryon assay. These data indicate that HHV-8 ORF 57 and IE63 possess certain common properties.
AlbrechtJ.-C.,
NicholasJ.,
BillerD.,
CameronK. R.,
BiesingerB.,
NewmanC.,
WittmannS.,
CraxtonM. A.,
ColemanH.,
FleckensteinB.,
HonessR. W.1992; Primary structure of the herpesvirus saimiri genome. Journal of Virology 66:5047–5058
ArvanitakisL.,
MesriE. A.,
NadorR. G.,
SaidJ. W.,
AschA. S.,
KnowlesD. M.,
CesarmanE.1996; Establishment and characterization of a primary effusion (body cavity-based) lymphoma cell line (BC-3) harboring Kaposi’s sarcoma-associated herpesvirus (KSHV/HHV-8) in the absence of Epstein–Barr virus. Blood 88:2648–2654
BoshoffC.,
GaoS. J.,
HealyL. E.,
MatthewsS.,
ThomasA. J.,
CoignetL.,
WarnkeR. A.,
StrauchenJ. A.,
MatutesE.,
KamelO. W.,
MooreP. S.,
WeissR. A.,
ChangY.1998; Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. Blood 91:1671–1679
BrownC. R.,
NakamuraM. S.,
MoscaJ. D.,
HaywardG. S.,
StrausS. E.,
PereraL. P.1995; Herpes simplex virus trans -regulatory protein ICP27 stabilizes and binds to 3′ ends of labile mRNA. Journal of Virology 69:7187–7195
BuissonM.,
HansF.,
KustersI.,
DuranN.,
SergeantA.1999; The C-terminal region but not the Arg-X-Pro repeat of Epstein–Barr virus protein EB2 is required for its effect on RNA splicing and transport. Journal of Virology 73:4090–4100
CesarmanE.,
ChangY.,
MooreP. S.,
SaidJ. W.,
KnowlesD. M.1995; Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. New England Journal of Medicine 332:1186–1191
CooperM.,
GoodwinD. J.,
HallK. T.,
StevensonA. J.,
MeredithD. M.,
MarkhamA. F.,
WhitehouseA.1999; The gene product encoded by ORF 57 of herpesvirus saimiri regulates the redistribution of the splicing factor SC-35. Journal of General Virology 80:1311–1316
DefechereuxP.,
DebrusS.,
BaudouxL.,
RentierB.,
PietteJ.1997; Varicella-zoster virus open reading frame 4 encodes an immediate-early protein with posttranscriptional regulatory properties. Journal of Virology 71:7073–7079
GaoS. J.,
KingsleyL.,
LiM.,
ZhengW.,
ParraviciniC.,
ZieglerJ.,
NewtonR.,
RinaldoC. R.,
SaahA.,
PhairJ.,
DetelsR.,
ChangY.,
MooreP. S.1996; KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi’s sarcoma. Nature Medicine 2:925–928
LukacD. M.,
RenneR.,
KirshnerJ. R.,
GanemD.1998; Reactivation of Kaposi’s sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology 252:304–312
McGeochD. J.,
CookS.,
DolanA.,
JamiesonF. E.,
TelfordE. A. R.1995; Molecular phylogeny and evolutionary timescale for the family of mammalian herpesviruses. Journal of Molecular Biology 247:443–458
MackettM.,
StewartJ. P.,
PepperS. de V.,
CheeM.,
EfstathiouS.,
NashA. A.,
ArrandJ. R.1997; Genetic content and preliminary transcriptional analysis of a representative region of murine gammaherpesvirus 68. Journal of General Virology 78:1425–1433
MooreP. S.,
GaoS. J.,
DominguezG.,
CesarmanE.,
LunguO.,
KnowlesD. M.,
GarberR.,
PellettP. E.,
McGeochD. J.,
ChangY.1996; Primary characterization of a herpesvirus agent associated with Kaposi’s sarcomae. Journal of Virology 70:549–558
NadorR. G.,
CesarmanE.,
KnowlesD. M.,
SaidJ. W.1995; Herpes-like DNA sequences in body-cavity-based lymphoma in an HIV-negative patient. New England Journal of Medicine 333:943
PhelanA.,
ClementsJ. B.1997; Herpes simplex virus type 1 immediate early protein IE63 shuttles between nuclear compartments and the cytoplasm. Journal of General Virology 78:3327–3331
PhelanA.,
Carmo-FonsecaM.,
McLaughlanJ.,
LamondA. I.,
ClementsJ. B.1993; A herpes simplex virus type 1 immediate-early gene product, IE63, regulates small nuclear ribonucleoprotein distribution. Proceedings of the National Academy of Sciences, USA 90:9056–9060
RussoJ. J.,
BohenzkyR. A.,
ChienM.-C.,
ChenJ.,
YanM.,
MaddalenaD.,
ParryJ. P.,
PeruzziD.,
EdelmanI. S.,
ChangY.,
MooreP. S.1996; Nucleotide sequence of the Kaposi’s sarcoma-associated herpesvirus (HHV8). Proceedings of the National Academy of Sciences USA 93:14862–14867
SampleJ.,
LanczG.,
NonoyamaM.1986; Mapping of genes in Bam HI fragment M of Epstein–Barr virus DNA that may determine the fate of viral infection. Journal of Virology 57:145–154
Sandri-GoldinR. M.1998a; ICP27 mediates HSV RNA export by shuttling through a leucine-rich nuclear export signal and binding viral intronless RNAs through an RGG motif. Genes & Development 12:868–879
SaridR.,
FloreO.,
BohenzkyR. A.,
ChangY.,
MooreP. S.1998; Transcription mapping of the Kaposi’s sarcoma-associated herpesvirus (human herpesvirus 8) genome in a body cavity-based lymphoma cell line (BC-1). Journal of Virology 72:1005–1012
SearlesR. P.,
BergquamE. P.,
AxthelmM. K.,
WongS. W.1999; Sequence and genomic analysis of a rhesus macaque rhadinovirus with similarity to Kaposi’s sarcoma-associated herpesvirus/human herpesvirus 8. Journal of Virology 73:3040–3053
SimpsonG. R.,
SchulzT. F.,
WhitbyD.,
CookP. M.,
BoshoffC.,
RainbowL.,
HowardM. R.,
GaoS. J.,
BohenzkyR. A.,
SimmondsP.,
LeeC.,
de RuiterA.,
HatzakisA.,
TedderR. S.,
WellerI. V.,
WeissR. A.,
MooreP. S.1996; Prevalence of Kaposi’s sarcoma associated herpesvirus infection measured by antibodies to recombinant capsid protein and latent immunofluorescence antigen. Lancet 348:1133–1138
SunR.,
LinS. F.,
GradovilleL.,
YuanY.,
ZhuF.,
MillerG.1998; A viral gene that activates lytic cycle expression of Kaposi’s sarcoma-associated herpesvirus. Proceedings of the National Academy of Sciences, USA 95:10866–10871
Sunil-ChandraN. P.,
EfstathiouS.,
ArnoJ.,
NashA. A.1992; Virological and pathological features of mice infected with murine gammaherpesvirus 68. Journal of General Virology 73:2347–2356
VaughanP. J.,
ThibaultK. J.,
HardwickeM. A.,
Sandri-GoldinR. M.1992; The herpes simplex virus immediate early protein ICP27 encodes a potential metal binding domain and binds zinc in vitro. Virology 189:377–384
WhitehouseA.,
CooperM.,
MeredithD. M.1998a; The immediate-early gene product encoded by open reading frame 57 of herpesvirus saimiri modulates gene expression at a posttranscriptional level. Journal of Virology 72:857–861
WinklerM.,
RiceS. A.,
StammingerT.1994; UL69 of human cytomegalovirus, an open reading frame with homology to ICP27 of herpes simplex virus, encodes a transactivator of gene expression. Journal of Virology 68:3943–3954