17 research outputs found

    Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

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    Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers

    Aterosklerozė: ląstelių komunikacijų pokyčiai

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    Objective. We investigated the distribution of atherosclerosis-linked genes within known metabolic / signaling pathways in order to determine most vulnerable pathways during atherosclerosis pathogenesis as well as to compile a full list of genes predominant for the disease. Materials and Methods. A search for genes associated with atherosclerosis within PubMed abstracts was carried out using modern data mining techniques available at SNPs3D database. Presence of data on metabolic pathways for each gene of interest was checked using KEGG and g-language tools. Association of atherosclerosis-linked genes within pathways was visualized and estimated using the g-language tool. Results. Analysis of to-date PubMed abstracts resulted in 748 human genes associated with atherosclerosis. Further analysis has revealed that 134 of over 300 known to date metabolic / signaling pathways include at least one gene associated with atherosclerosis of the total of 436 genes. Reducing accident ascription pathways populated by at least 10 atherosclerosis- linked genes were only taken into account making final conclusions. Conclusions. Taken together, our results demonstrate that the essence of atherosclerosis is the dysfunction of cell signaling and intercell communication cascades. We maintain an exclusively high role of cytokines and their receptors in atherosclerosis pathogenesis. A sufficiently high intersection of atherosclerosis and diabetes or several cancer species proposed an increased risk for further complications in these patients

    Evaluation of trichodysplasia spinulosa-associated polyomavirus capsid protein as a new carrier for construction of chimeric virus-like particles harboring foreign epitopes

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    Recombinant virus-like particles (VLPs) represent a promising tool for protein engineering. Recently, trichodysplasia spinulosa-associated polyomavirus (TSPyV) viral protein 1 (VP1) was efficiently produced in yeast expression system and shown to self-assemble to VLPs. In the current study, TSPyV VP1 protein was exploited as a carrier for construction of chimeric VLPs harboring selected B and T cell-specific epitopes and evaluated in comparison to hamster polyomavirus VP1 protein. Chimeric VLPs with inserted either hepatitis B virus preS1 epitope DPAFR or a universal T cell-specific epitope AKFVAAWTLKAAA were produced in yeast Saccharomyces cerevisiae. Target epitopes were incorporated either at the HI or BC loop of the VP1 protein. The insertion sites were selected based on molecular models of TSPyV VP1 protein. The surface exposure of the insert positions was confirmed using a collection of monoclonal antibodies raised against the intact TSPyV VP1 protein. All generated chimeric proteins were capable to self-assemble to VLPs, which induced a strong immune response in mice. The chimeric VLPs also activated dendritic cells and T cells as demonstrated by analysis of cell surface markers and cytokine production profiles in spleen cell cultures. In conclusion, TSPyV VP1 protein represents a new potential carrier for construction of chimeric VLPs harboring target epitopes

    Identification of Two Novel Members of the Tentative Genus <i>Wukipolyomavirus</i> in Wild Rodents

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    <div><p>Two novel polyomaviruses (PyVs) were identified in kidney and chest-cavity fluid samples of wild bank voles (<i>Myodes glareolus</i>) and common voles (<i>Microtus arvalis</i>) collected in Germany. All cloned and sequenced genomes had the typical PyV genome organization, including putative open reading frames for early regulatory proteins large T antigen and small T antigen on one strand and for structural late proteins (VP1, VP2 and VP3) on the other strand. Virus-like particles (VLPs) were generated by yeast expression of the VP1 protein of both PyVs. VLP-based ELISA and large T-antigen sequence-targeted polymerase-chain reaction investigations demonstrated signs of infection of these novel PyVs in about 42% of bank voles and 18% of common voles. In most cases only viral DNA, but not VP1-specific antibodies were detected. In additional animals exclusively VP1-specific antibodies, but no viral DNA was detected, indicative for virus clearance. Phylogenetic and clustering analysis including all known PyV genomes placed novel bank vole and common vole PyVs amongst members of the tentative <i>Wukipolymavirus</i> genus. The other known four rodent PyVs, Murine PyV and Hamster PyV, and Murine pneumotropic virus and Mastomys PyV belong to different phylogenetic clades, tentatively named <i>Orthopolyomavirus</i> I and <i>Orthopolyomavirus</i> II, respectively. In conclusion, the finding of novel vole-borne PyVs may suggest an evolutionary origin of ancient wukipolyomaviruses in rodents and may offer the possibility to develop a vole-based animal model for human wukipolyomaviruses.</p></div

    Phylogenetic tree of 98 representatives of <i>Polyomaviridae</i> family obtained using ML methods for concatenated LTag, STag, VP1 and VP2 protein sequence alignment.

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    <p>The tree is rooted at the most distant PyVs, namely fish polyomaviruses. Numbers at the nodes indicate statistical support (bootstrap values) for branch placements. Red triangles mark taxons with least confidence in their placement, as determined using RogueNaRok. The five lineages: <i>Orthopolyomavirus I</i>, <i>Orthopolyomavirus II</i>, <i>Avipolyomavirus</i>, <i>Malawipolyomavirus</i> and <i>Wukipolyomavirus</i> are highlighted in different colors. Rodent polyomaviruses Murine PyV (MPyV), Hamster PyV (HaPyV), Murine pneumotropic virus (MPtV) and Mastomys PyV (MasPyV) are labeled in green. The novel viruses BVPyV and CVPyV are labeled in blue.</p

    Schematic presentation of the genome organization of BVPyV (A) and CVPyV (B) and alignment of ORI region sequences of BVPyV strains (KS/14/281 and KS/13/999) and CVPyV strain KS/13/947 (C).

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    <p>The positions of LTag introns are shown uncolored. Putative LTag binding sites (GAGGC pentanucleotides) are shown in red; AT-rich region/TATA box is shown in green; palindromic repeats shown in magenta; early palindrome (EP) region is underlined; LTag ATG codon is shown in blue (according [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140916#pone.0140916.ref038" target="_blank">38</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140916#pone.0140916.ref039" target="_blank">39</a>]).</p

    Sliding window analysis of genome sequences specific to CVPyV and BVPyV compared to other PyVs (%).

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    <p>The short fragments of a length w = 50 nt of BVPyV and CVPyV genomes were compared with w-mers of all PyV genomes by means of a sliding-window procedure. Only pairs of w-mers which had higher count of identical nucleotides in their alignment than some predefined critical value n = 30 when aligned were determined as similar. VP1, VP2, VP3, LTag, and STag genes are labeled with different colors. The nucleotide positions in genome are indicated at the bottom.</p
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