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Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene.

ABSTRACT: BACKGROUND: The genus Orbivirus includes several species that infect livestock - including Bluetongue virus (BTV) and African horse sickness virus (AHSV). These viruses have linear dsRNA genomes divided into ten segments, all of which have previously been assumed to be monocistronic. RESULTS: Bioinformatic evidence is presented for a short overlapping coding sequence (CDS) in the Orbivirus genome segment 9, overlapping the VP6 cistron in the +1 reading frame. In BTV, a 77-79 codon AUG-initiated open reading frame (hereafter ORFX) is present in all 48 segment 9 sequences analysed. The pattern of base variations across the 48-sequence alignment indicates that ORFX is subject to functional constraints at the amino acid level (even when the constraints due to coding in the overlapping VP6 reading frame are taken into account; MLOGD software). In fact the translated ORFX shows greater amino acid conservation than the overlapping region of VP6. The ORFX AUG codon has a strong Kozak context in all 48 sequences. Each has only one or two upstream AUG codons, always in the VP6 reading frame, and (with a single exception) always with weak or medium Kozak context. Thus, in BTV, ORFX may be translated via leaky scanning. A long (83-169 codon) ORF is present in a corresponding location and reading frame in all other Orbivirus species analysed except Saint Croix River virus (SCRV; the most divergent). Again, the pattern of base variations across sequence alignments indicates multiple coding in the VP6 and ORFX reading frames. CONCLUSION: At approximately 9.5 kDa, the putative ORFX product in BTV is too small to appear on most published protein gels. Nonetheless, a review of past literature reveals a number of possible detections. We hope that presentation of this bioinformatic analysis will stimulate an attempt to experimentally verify the expression and functional role of ORFX, and hence lead to a greater understanding of the molecular biology of these important pathogens.

SUBMITTER: Firth AE

PROVIDER: S-EPMC2373779 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene.

Firth Andrew E AE

Virology journal 20080414

<h4>Background</h4>The genus Orbivirus includes several species that infect livestock - including Bluetongue virus (BTV) and African horse sickness virus (AHSV). These viruses have linear dsRNA genomes divided into ten segments, all of which have previously been assumed to be monocistronic.<h4>Results</h4>Bioinformatic evidence is presented for a short overlapping coding sequence (CDS) in the Orbivirus genome segment 9, overlapping the VP6 cistron in the +1 reading frame. In BTV, a 77-79 codon A ...[more]

PMID: 18489030

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Project description:BACKGROUND:Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear. METHODS:This study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment. RESULTS:Totally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy. CONCLUSIONS:Our study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.

Dataset Information

Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene.

Publications

Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene.

Similar Datasets

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