No abstract

This report describes the complete nucleotide sequence of the genome of herpesvirus saimiri, the prototype of gammaherpesvirus subgroup 2 (rhadinoviruses). The unique low-G+C-content DNA region has 112,930 bp with an average base composition of 34.5% G+C and is flanked by about 35 noncoding high-G+C-content DNA repeats of 1,444 bp (70.8% G+C) in tandem orientation. We identified 76 major open reading frames and a set of seven U-RNA genes for a total of 83 potential genes. The genes are closely arranged, with only a few regions of sizable noncoding sequences. For 60 of the predicted proteins, homologous sequences are found in other herpesviruses. Genes conserved between herpesvirus saimiri and Epstein-Barr virus (gammaherpesvirus subgroup 1) show that their genomes are generally collinear, although conserved gene blocks are separated by * Corresponding author. t This article is dedicated to the memory of Robert W. Honess, who initiated this endeavor and died before its completion.

Sequencing studies have indicated that the unique component of the human herpesvirus 6 (HHV-6) genome and the unique long segment of the human cytomegalovirus genome are genetically colinear. Of particular interest is the identification of a region of local CpG dinucleotide suppression in the genome of HHV-6, a feature conserved in the genomes of human cytomegalovirus, murine cytomegalovirus, and simian cytomegalovirus, and a characteristic of the major immediate-early loci of these viruses. Adjacent to this region in HHV-6 are approximately 30 copies of a 103- to 108-bp sequence element, which contains consensus binding sites for the transcription factors AP2 and NF kappa B, in addition to a single KpnI recognition site. Together, these KpnI repeat units may compose an immediate-early enhancer, analogous to those found in the cytomegaloviruses. We present the sequence of this region of HHV-6 and demonstrate that a transactivating function is encoded by this region. We have used polymerase chain reaction to synthesize fragments containing open reading frames and 5' sequences with or without the upstream KpnI repeat units. Effector plasmids containing these HHV-6 coding and 5' sequences were able to effect activation of heterologous promoter-chloramphenicol acetyltransferase (CAT) constructs, including adenovirus E3-CAT and E4-CAT, human T-cell lymphotropic virus type I long terminal repeat (LTR)-CAT, and human immunodeficiency virus LTR-CAT, in cotransfection experiments in Vero cells and peripheral blood lymphocytes. Furthermore, we have identified the major open reading frame (RF4; 2.3 kb) as being essential for activation, and we have shown that the NF kappa B, SP1, and TATA box motifs in the human immunodeficiency virus LTR are all required for full induction of the promoter by the HHV-6-encoded transactivator.

Summary Safety of administration of a vindesine (VDS)-anti-CEA conjugate and its ability to localise after radiolabelling were investigated in patients with advanced metastatic carcinoma (4 colorectal and 4 ovarian).

We have reported previously the detection of two stable immediate-early (IE) transcripts that accumulate in cycloheximide-treated cells infected with herpesvirus saimiri (HVS). These are the 1.6-kb mRNA from the 52-kDa gene (which is homologous to the BSLF2-BMLF1 gene of Epstein-Barr virus) and the 1.3-kb mRNA from the HindM-G fragment of virus DNA. In order to study the roles of the HVS IE gene products in the progression of a lytic infection, the promoter region of the delayed-early 110-kDa gene of HVS was sequenced, the transcription initiation site was mapped by RNase protection, and the promoter sequences were cloned upstream of the chloramphenicol acetyltransferase (CAT) gene. Sequences between -447 and +37 (relative to the 110-kDa transcription initiation site) were sufficient for response to HVS superinfection of transfected cells, but the 110-kDa promoter was activated only poorly by the 52-kDa and HindIll-G IE (IE-G) proteins in cotransfection experiments. However, a distinct region of the genome, EcoRI-D (15 kbp), was able to activate 110-kDa-CAT expression relatively efficiently in similar experiments. A 4.7-kbp PstI fragment encoding this function was isolated and sequenced, and further subcloning identified the gene encoding the EcoRI-D trans activator. This gene, which we now designate HVS.R, is homologous to the BRLFl-encoded transcriptional effector of Epstein-Barr virus.