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L Yuen

Publications and source records attributed to L Yuen.

32 records · Page 2Linked to original sources

Identification and sequencing of the spheroidin gene of Choristoneura biennis entomopoxvirus.

Entomopoxviruses are a class of insect viruses whose virions are embedded in cytoplasmic occlusion bodies. The major component of these protective complexes is a protein called spheroidin. An open reading frame encoding the spheroidin gene of Choristoneura biennis entomopoxvirus has been identified and sequenced in our laboratory. This protein coding region is 1023 nucleotides long and specifies a polypeptide of 38,500 Da. Spheroidin was purified by SDS polyacrylamide gel electrophoresis, electroeluted, and its amino terminus sequence was determined on a gas phase sequencer. We observed that the first 20 N-terminal amino acids were absent in the mature processed form of the spheroidin molecule. Examination of these 20 residues revealed their hydrophobic nature and close resemblance to the consensus signal peptide sequence which is commonly found on membrane proteins. The DNA sequence of the spheroidin gene predicted a processed polypeptide with a molecular weight of 36 kDa. However, spheroidin was observed to aggregate in complexes composed of 50-kDa monomers. Intermolecular disulfide bonds were shown to play major roles in the formation and structure of these viral occlusion bodies. The difference in molecular weight between the predicted protein and its counterpart in infected cells is likely due to post-translational modifications. Indeed, two potential asparagine-linked glycosylation sites are present on the spheroidin molecule. The 5' flanking regions of the spheroidin gene and the vaccinia major core protein precursor gene P4b were shown to share substantial homology.

Amino Acid Sequence↗

Identification and characterization of a baculovirus occlusion body glycoprotein which resembles spheroidin, an entomopoxvirus protein.

A 37-kDa polypeptide specified by Autographa californica nuclear polyhedrosis virus was found to share significant homology with Choristoneura biennis entomopoxyvirus spheroidin protein, which is the major component of entomopoxvirus occlusion bodies. Antibodies raised against spheroidin cross-reacted with the 37-kDa protein and confirmed its expression in the late phase of wild-type baculovirus infection. Immunoblot analysis and fluorescence microscopy demonstrated that the protein was associated with purified A. californica nuclear polyhedrosis virus occlusion bodies and was absent in purified virions. Immunofluorescence studies localized the protein to the periphery of occlusion bodies and the internal membranes of cells infected with wild-type baculovirus. The open reading frame encoding this spheroidinlike protein was inserted into a baculovirus expression vector, and recombinant protein was synthesized under control of the polyhedrin promoter. Studies of the recombinant protein demonstrated that it was heterogeneous in molecular mass as a result of N-linked glycosylation. Tunicamycin inhibited carbohydrate addition and yielded proteins of 34 and 33 kDa.

Amino Acid Sequence↗

Permeability changes at blood-retinal barrier in diabetes and effect of aldose reductase inhibition.

Sensitive quantitative in vivo techniques were used to assess the permeability at the blood-retinal barrier (BRB) to [14C]sucrose in the anesthetized streptozocin-diabetic rat at various time points (3 wk, 6 mo, 13 mo) after induction of diabetes. The effects of concomitant administration of an aldose reductase inhibitor (ARI) on sorbitol levels in the retina and on BRB permeability were also measured. No increase in BRB permeability was found in rats diabetic for 3 wk or 6 mo, but after 13 mo of hyperglycemia there was an increase in permeability of 240%. No effect on permeability was seen in diabetic animals given the ARI despite the retinal sorbitol levels being decreased in the treated compared with the untreated diabetic group fed a normal diet. This study suggests that the accumulation of sorbitol within the cells of the BRB is not responsible for the breakdown of BRB permeability seen after 7-13 mo of hyperglycemia and that the enzyme aldose reductase is not involved in its pathogenesis.

Aldehyde Reductase↗

A high capacity, reusable oligodeoxythymidine affinity column.

A high capacity, reusable oligodeoxythymidine (oligo(dT)) affinity column suitable for purification of polyadenylated mRNA is described. Oligo(dT) molecules, 30 nucleotides in length, were chemically synthesized on an Applied Biosystems DNA synthesizer. Deprotection of the oligo(dT) molecules was achieved by thiophenol/dioxane/triethylamine treatment. Since no hot ammonia treatment was required, the oligo(dT) molecules remained covalently attached to the support matrix. The resulting column has very high oligo(dT) density and can be used directly for purifying polyadenylated mRNA. Column-purified mRNAs were shown to be intact and functional in Northern blot analysis, in vitro translation, and reverse transcription assays.

Animals↗

Purification of a factor required for transcription of vaccinia virus early genes.

Partially purified DNA-dependent RNA polymerase from infectious vaccinia virus particles exhibits the following two activities: 1) specific transcription of double-stranded DNA templates containing vaccinia early promoters and 2) nonspecific transcription of single-stranded DNA templates. After further purification of the RNA polymerase, specific transcriptase activity was selectively diminished suggesting the loss of a transcription factor. In agreement with the latter hypothesis, transcriptase activity could be reconstituted by mixing the purified RNA polymerase with certain column fractions. A quantitative complementation assay was developed and used to locate the transcription factor during successive column chromatography steps. The factor eluted as a single peak of activity from single strand DNA-cellulose and phosphocellulose columns. An observation that the transcription factor binds specifically to vaccinia early promoter sequences was exploited in the final affinity chromatography steps. The purified factor was separated from all previously identified vaccinia enzymes and contained two polypeptides of Mr 77,000 and 82,000. A DNA-dependent ATPase activity also copurified with the transcription factor. Although a single template was used for assays during isolation, the purified factor stimulated transcription of three other early genes by 20-30-fold suggesting that it has a general role in conferring promoter specificity for initiation of early transcription.

Chromatography, Affinity↗

Early promoter-binding factor from vaccinia virions.

A factor, present in transcriptionally active extracts prepared from purified vaccinia virus particles, binds to vaccinia early promoter sequences. The specificity of binding was demonstrated by electrophoretic mobility shift assays using the 5'-terminal segments of two early genes and related and unrelated competitor DNA fragments. DNase I "footprint" analysis indicated that the factor formed a complex with promoter regions of both genes and protected sequences of 10-15 nucleotides centered 21-24 nucleotides upstream of the RNA start sites. The lack of protection of a late regulatory sequence and of an early promoter with transcriptionally inactivating single-nucleotide substitutions suggested that the protein is an early transcription factor. When subjected to glycerol gradient centrifugation, the DNA-binding factor was resolved from RNA polymerase and sedimented as a 7.5S species with an estimated molecular weight of 130,000.

Binding Sites↗

Oligonucleotide sequence signaling transcriptional termination of vaccinia virus early genes.

In an in vitro system containing enzymes extracted from vaccinia virions, transcription of the vaccinia growth factor gene terminated approximately 50 base pairs downstream of a thymidine-rich sequence. Deletion mutagenesis suggested the presence of two tandem termination signals. The signal was identified by replacing the 3' end of the gene with the oligonucleotide AATTTTTAT that induced downstream termination. Further analysis of the transcripts formed with a series of templates containing 16 related synthetic oligonucleotides established the minimum functional termination signal as TTTTTNT, in which N represents any nucleotide. Termination efficiency may be increased, however, by the presence of an adenosine preceding the thymidine cluster. The general use of this signal at early times in infection but not at late times is supported by a survey of vaccinia virus gene sequences.

Base Sequence↗

Transcription of vaccinia virus early genes by enzymes isolated from vaccinia virions terminates downstream of a regulatory sequence.

We describe an in vitro transcription system in which the polyadenylated 3' ends of vaccinia virus mRNAs are formed by termination downstream of a regulatory signal. When linear DNA templates containing vaccinia early genes were incubated with soluble enzymes extracted from vaccinia virions, mature-size mRNAs were synthesized within 1 min, whereas longer run-off transcripts were not detected until later. Deleting a series of thymidylate residues located downstream of the coding region abolished termination. The 3' ends of the transcripts formed heterogeneously, between 50 and 70 nucleotides past the T-rich termination signal, in either viral- or vector-derived sequences. Polyadenylation of the transcripts occurred without regard to the terminal sequence and was inhibited by adding exogenous RNA. Although exogenous RNAs were also polyadenylated, processing of 3' ends was not observed.

Base Sequence↗

Multiple 3' ends of mRNA encoding vaccinia virus growth factor occur within a series of repeated sequences downstream of T clusters.

Analysis of the 5' ends of six apparently full-length cloned cDNA copies of the vaccinia virus growth factor gene suggested precise transcriptional initiation at the first purine following a run of five pyrimidines in the noncoding strand. By contrast, the 3' ends exhibited heterogeneity and were distributed over a 46-base-pair region. In each of the six cDNAs, the nucleotide immediately preceding the retained copy of the poly(A) tail corresponded to the first or second T of a TATGT repeat. Clusters of Ts occurred upstream of the 3' ends, but the AATAAA polyadenylation consensus sequence of higher eucaryotes was absent. Determination of the complete sequence of one cDNA revealed exact correspondence with the vaccinia virus growth factor gene, indicating the absence of internal RNA processing.

Base Sequence↗