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U A Gompels

Publications and source records attributed to U A Gompels.

28 records · Page 2Linked to original sources
PubMed1990

Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein-Barr virus and herpesvirus saimiri.

Short nucleotide sequence analysis of seven restriction fragments of murine herpesvirus 68 (MHV-68) DNA has been undertaken and used to determine the overall genome organization and relatedness of this virus to other well characterized representatives of the alpha-, beta- and gammaherpesvirus subgroups. Nine genes have been identified which encode amino acid sequences with greater similarity to proteins of the gammaherpesvirus Epstein-Barr virus (EBV) than to the homologous products of the alphaherpesviruses varicella-zoster virus and herpes simples virus type 1 or the betaherpesvirus human cytomegalovirus. In addition, the genome organization of MHV-68 is shown to have an overall collinearity with that of the gammaherpesviruses EBV and herpesvirus saimiri. In common with these viruses, dinucleotide frequency analysis of MHV-68 coding sequences reveals a marked reduction in CpG dinucleotide frequency thus implicating a dividing cell population as the site of latency in vivo.

Amino Acid Sequence↗
PubMed1990

Human herpesvirus 6 is closely related to human cytomegalovirus.

A sequence of 21,858 base pairs from the genome of human herpesvirus 6 (HHV-6) strain U1102 is presented. The sequence has a mean composition of 41% G + C, and the observed frequency of CpG dinucleotides is close to that predicted from this mononucleotide composition. The sequence contains 17 complete open reading frames (ORFs) and part of another at the 5' end of the sequence. The predicted protein products of two of these ORFs have no recognizable homologs in the genomes of other sequenced human herpesviruses (i.e., Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], herpes simplex virus [HSV], and varicella-zoster virus [VZV]). However, the products of nine other ORFs are clearly homologous to a set of genes that is conserved in all other sequenced herpesviruses, including homologs of the alkaline exonuclease, the phosphotransferase, the spliced ORF, and the major capsid protein genes. Measurements of similarity between these homologous sequences showed that HHV-6 is clearly most closely related to HCMV. The degree of relatedness between HHV-6 and HCMV was commensurate with that observed in comparisons between HSV and VZV or EBV and herpesvirus saimiri and significantly greater than its relatedness to EBV, HSV, or VZV. In addition, the gene for the major capsid protein and its 5' neighbor are reoriented with respect to the spliced ORFs in the genomes of both HHV-6 and HCMV relative to the organization observed in EBV, HSV, and VZV. Three ORFs in HHV-6 have recognizable homologs only in the genome of HCMV. Despite differences in gross composition and size, we conclude that the genomes of HHV-6 and HCMV are closely related.

Amino Acid Sequence↗
PubMed1989

A comparative analysis of the sequence of the thymidine kinase gene of a gammaherpesvirus, herpesvirus saimiri.

We present the nucleotide sequence of a region from the genome of the A + T-rich gammaherpesvirus, herpesvirus saimiri (HVS), which includes the coding sequences for the viral thymidine kinase (TK) gene. The organization of genes in this region resembles the homologous region of the Epstein-Barr virus (EBV) genome and is very compact, using overlapping coding sequences and with nucleotides shared by initiation and termination codons of neighbouring reading frames. The HVS TK is predicted to contain a 527 residue polypeptide with the first part of the presumptive nucleotide-binding site [(L, I, V)(F, Y)(I, L)(D, E)(G)(X)(X)(G)(L, I, V, M)(G)(K)(T, S)(T, S)] located at residues 212 to 224. This motif is close to the amino terminus of the TK polypeptides of alphaherpesviruses and the polypeptides of the cellular and poxvirus-encoded enzymes. The corresponding reading frame of the human gammaherpesvirus (EBV) also has a long amino-terminal extension but significant amino acid sequence similarities between the HVS and EBV sequences are not observed until the region of the nucleotide-binding site. Comparisons of these homologous carboxy-terminal sequences of the HVS- and EBV-encoded proteins with those from six alphaherpes viruses and proteins encoded by Marek's disease virus (MDV) and the herpesvirus of turkeys (HVT) confirm that the HVS and EBV sequences are products of a distinct lineage. The sequences of alphaherpesvirus enzymes than to those of HVS and EBV. Comparison of these 10 highly divergent TK sequences extends and refines the identification of essential features of this family of herpesvirus enzymes and defines 19 positions at which all sequences have identical residues.

Amino Acid Sequence↗
PubMed1989

Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes.

The DNA sequences of genomes from G + C-rich and A + T-rich lymphotropic herpesviruses [i.e. gammaherpesviruses; Epstein-Barr virus and herpesvirus saimiri (HVS)] are deficient in CpG dinucleotides and contain an excess of TpG and CpA dinucleotides relative to frequencies predicted from their mononucleotide compositions. In contrast, for sequences from genomes of G + C-rich and A + T-rich neurotropic herpesviruses (i.e. alphaherpesviruses; herpes simplex virus and varicellazoster virus) and human cytomegalovirus (HCMV; a betaherpesvirus) the mean observed frequencies of these dinucleotides are close to those expected from their mononucleotide compositions. Comparisons between DNA sequences that encode proteins conserved in all these viruses also show that sequences of these lymphotropic viruses are CpG-deficient whereas the homologous genes from the neurotropic viruses and the HCMV are not. Analyses of local variations in dinucleotide frequencies reveal some occurrences of clustered CpG dinucleotides in generally deficient genomes (e.g. upstream of the thymidylate synthase gene of HVS) and locally CpG-deficient regions within some generally non-deficient genomes (e.g. the major immediate early genes of human, simian and murine CMVs). A relative deficiency in CpG and an excess of TpG and CpA dinucleotides is a diagnostic feature of higher eukaryotic DNA sequences that have been subjected to methylation of cytosine residues in CpG doublets with the resulting increase in mutations to give TpG (and thereby its complement, CpA). The available evidence implicates the latent genome as the site of methylation of these herpesviruses. We conclude that in the neurotropic herpesviruses the normal latent precursors to infectious progeny are not methylated whereas there is local methylation of the immediate early locus in the latent genomes of CMVs, and the latent genomes of these lymphotropic herpesviruses are extensively methylated.

Base Sequence↗
PubMed1989

Antigenic properties and cellular localization of herpes simplex virus glycoprotein H synthesized in a mammalian cell expression system.

Herpes simplex virus type 1 glycoprotein H (HSV-1 gH) was synthesized in an inducible mammalian cell expression system, and its properties were examined. The gH coding sequence, together with the stable 5' untranslated leader sequence from xenopus beta-globin, was placed under control of the strong promoter from the human cytomegalovirus major immediate-early gene in an amplifiable plasmid which contains the simian virus 40 (SV40) virus origin for replication (ori). This expression vector was transfected into ts COS cells constitutively expressing a temperature-sensitive SV40 T antigen which allows utilization of the SV40 ori at permissive temperatures. The results of transient expression assays at the permissive temperature showed that HSV-1 gH could be synthesized in greater amounts than those produced by a high-multiplicity virus infection. The proteins produced were detected in Western blots (immunoblots) with a HSV-1 gH-specific polyclonal serum raised against a TrpE-gH fusion protein. The transfected gH had an apparent molecular weight of approximately 105,000, intermediate in size to those of the precursor (100,000) and fully processed forms (110,000) of HSV-1 gH from infections. Antigenicity was investigated by reactions with three virus-neutralizing monoclonal antibodies specific for conformational epitopes on gH. Only one of these monoclonal antibodies could immunoprecipitate the synthesized gH. However, equal recognition of the transfected gH was achieved by superinfection with virus. In addition, detectable amounts of gH were not expressed on the cell surface unless the cells were superinfected with virus. Studies with a temperature-sensitive mutant, ts1201, defective in encapsidation showed that the changes in antigenic structure and cell surface expression caused by superinfection with virus were not due simply to incorporation of gH into virions. These results suggest that gH requires additional virus gene products for cell surface localization and formation of an antigenic structure important for its function in mediating infectivity.

Animals↗
PubMed1988

Conservation of glycoprotein H (gH) in herpesviruses: nucleotide sequence of the gH gene from herpesvirus saimiri.

We present the nucleotide sequence of the glycoprotein H (gH) gene of herpesvirus saimiri (HVS), a representative of the T lymphotropic herpesviruses of New World monkeys, and compare the predicted amino acid sequence with sequences of homologous proteins from four human herpesviruses. The HVS gH gene is located within a block of genes encoding products conserved in all herpesvirus subgroups as represented by the human herpesviruses herpes simplex virus, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus. In agreement with the biological grouping of HVS as a lymphotropic gammaherpesvirus, its gH amino acid sequence shows greatest similarity to that of the B lymphotropic Epstein-Barr virus, although the nucleotide sequences of their respective gH genes show little similarity given different G + C compositions of 31% and 54%. The similarity observed between the gH amino acid sequences of the two representative gammaherpesviruses is greater than that between the two human alphaherpesviruses varicella-zoster virus and herpes simplex virus. The members of the gH family range in size from 706 to 743 amino acid residues for the beta- and gammaherpesviruses, to 838 to 841 for the alphaherpesviruses, giving non-glycosylated precursors with Mr values of 78,322 to 93,651. The difference in size is due to heterogeneity in the poorly conserved N-terminal regions of the larger alphaherpesviruses compared to the smaller beta- and gammaherpesvirus molecules. Greatest similarity is observed in the C-terminal halves of the proteins including residues surrounding four conserved cysteine residues, a conserved N-linked glycosylation site (within the sequence NGTV) 13 to 18 residues proximal to the membrane-spanning sequences, and a short cytoplasmic domain of seven or eight residues for the beta- and gammaherpesviruses' and 14 or 15 residues for the alphaherpesviruses' gH. Thus, the representatives of all subgroups of herpesviruses, including those with a non-human host, encode gH homologues. Together with the observation that gH of these viruses are major targets for virus neutralization by antibody, this suggests that this glycoprotein family is essential among all herpesviruses and represents a major component involved in herpesvirus infectivity.

Amino Acid Sequence↗
PubMed1988

Conservation of gene organization in the lymphotropic herpesviruses herpesvirus Saimiri and Epstein-Barr virus.

By analyses of short DNA sequences, we have deduced the overall arrangement of genes in the (A + T)-rich coding sequences of herpesvirus saimiri (HVS) relative to the arrangements of homologous genes in the (G + C)-rich coding sequences of the Epstein-Barr virus (EBV) genome and the (A + T)-rich sequences of the varicella-zoster virus (VZV) genome. Fragments of HVS DNA from 13 separate sites within the 111 kilobase pairs of the light DNA coding sequences of the genome were subcloned into M13 vectors, and sequences of up to 350 bases were determined from each of these sites. Amino acid sequences predicted for fragments of open reading frames defined by these sequences were compared with a library of the protein sequences of major open reading frames predicted from the complete DNA sequences of VZV and EBV. Of the 13 short amino acid sequences obtained from HVS, only 3 were recognizably homologous to proteins encoded by VZV, but all 13 HVS sequences were unambiguously homologous to gene products encoded by EBV. The HVS reading frames identified by this method included homologs of the major capsid polypeptides, glycoprotein H, the major nonstructural DNA-binding protein, thymidine kinase, and the homolog of the regulatory gene product of the BMLF1 reading frame of EBV. Locally as well as globally, the order and relative orientation of these genes resembled that of their homologs on the EBV genome. Despite the major differences in their nucleotide compositions and in the nature and arrangements of reiterated DNA sequences, the genomes of the lymphotropic herpesviruses HVS and EBV encode closely related proteins, and they share a common organization of these coding sequences which differs from that of the neurotropic herpesviruses, VZV and herpes simplex virus.

Amino Acid Sequence↗
PubMed1988

Conservation of sequence and function between the product of the 52-kilodalton immediate-early gene of herpesvirus saimiri and the BMLF1-encoded transcriptional effector (EB2) of Epstein-Barr virus.

We present a sequence of 2,220 nucleotides from a region of the genome of herpesvirus saimiri (HVS) which includes the coding and putative regulatory sequences for the 52-kilodalton (kDa) immediate-early (IE) phosphoprotein of the virus. The amino acid sequence predicted for this protein shows it to be homologous to the EB2 transcriptional effector encoded by the BMLF1 open reading frame of Epstein-Barr virus (EBV), the IE 68-kDa protein of varicella-zoster virus, and the IE 63-kDa (alpha 27) protein of herpes simplex virus (HSV). By measuring the function of the HVS 52-kDa-protein gene in transient expression assays, we also showed that it can substitute with comparable efficiency for the EB2 product of EBV in the EB1-dependent activation of the EBV DR promoter. The alpha 27 gene of HSV was an inefficient trans-activator in similar assays. We conclude that the IE 52-kDa protein of HVS is structurally and functionally more similar to the homologous protein of the human lymphotropic virus, EBV, than to the corresponding proteins from the neurotropic viruses, varicella-zoster virus and HSV.

Amino Acid Sequence↗