Age- and Disease-Dependent HERV-W Envelope Allelic Variation in Brain: Association with Neuroimmune Gene Expression
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{"title"=>"Age- and disease-dependent HERV-W envelope allelic variation in brain: Association with neuroimmune gene expression", "type"=>"journal", "authors"=>[{"first_name"=>"Rakesh K.", "last_name"=>"Bhat", "scopus_author_id"=>"56371449000"}, {"first_name"=>"Kristofor K.", "last_name"=>"Ellestad", "scopus_author_id"=>"6506638357"}, {"first_name"=>"B. Matt", "last_name"=>"Wheatley", "scopus_author_id"=>"36939639800"}, {"first_name"=>"Rene", "last_name"=>"Warren", "scopus_author_id"=>"8779272500"}, {"first_name"=>"Robert A.", "last_name"=>"Holt", "scopus_author_id"=>"7402085535"}, {"first_name"=>"Christopher", "last_name"=>"Power", "scopus_author_id"=>"47061915900"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-79955712708", "pmid"=>"21559469", "sgr"=>"79955712708", "doi"=>"10.1371/journal.pone.0019176", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"361724295"}, "id"=>"02ca0241-a17f-31e0-b55b-1b60e872e7ab", "abstract"=>"BACKGROUND: The glycoprotein, Syncytin-1, is encoded by a human endogenous retrovirus (HERV)-W env gene and is capable of inducing neuroinflammation. The specific allele(s) responsible for Syncytin-1 expression in the brain is uncertain. Herein, HERV-W env diversity together with Syncytin-1 abundance and host immune gene profiles were examined in the nervous system using a multiplatform approach.\\n\\nRESULTS: HERV-W env sequences were encoded by multiple chromosomal encoding loci in primary human neurons compared with less chromosomal diversity in astrocytes and microglia (p<0.05). HERV-W env RNA sequences cloned from brains of patients with systemic or neurologic diseases were principally derived from chromosomal locus 7q21.2. Within the same specimens, HERV-W env transcript levels were correlated with the expression of multiple proinflammatory genes (p<0.05). Deep sequencing of brain transcriptomes disclosed the env transcripts to be the most abundant HERV-W transcripts, showing greater expression in fetal compared with healthy adult brain specimens. Syncytin-1's expression in healthy brain specimens was derived from multiple encoding loci and linked to distinct immune and developmental gene profiles.\\n\\nCONCLUSIONS: Syncytin-1 expression in the brain during disease was associated with neuroinflammation and was principally encoded by a full length provirus. The present studies also highlighted the diversity in HERV gene expression within the brain and reinforce the potential contributions of HERV expression to neuroinflammatory diseases.", "link"=>"http://www.mendeley.com/research/age-diseasedependent-hervw-envelope-allelic-variation-brain-association-neuroimmune-gene-expression", "reader_count"=>31, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Librarian"=>2, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Librarian"=>2, "Researcher"=>9, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>2, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>5, "Neuroscience"=>2, "Psychology"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Iran"=>1, "United States"=>1, "United Kingdom"=>1, "Italy"=>1, "Portugal"=>1, "Germany"=>1}, "group_count"=>4}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/778884"], "description"=>"<p>(<b>A</b>) (<b>i</b>) Ethidium-stained agarose gel of amplicons after second PCR step from fetal (F) and adult (A) brain samples. (<b>ii</b>) Relative clonal frequency of transcriptionally active HERV-W <i>env</i> sequences in fetal and adult brain samples showing encoding loci to be 7q21.2 and other sites. Diversity relative to ERVWE1 is displayed in parenthesis. (<b>B</b>) Chromosomal loci distribution of transcriptionally active HERV-W <i>env</i> sequences in fetal and adult brain samples. (<b>C</b>) Heatmap of gene expression was generated from RNA tags obtained by deep sequencing analysis by selecting a set of host genes relevant to neuroinflammation and associated with HERV-W <i>env</i> abundance in the sample. Over-expressed genes are shown in red and under-expressed in blue. (<b>D</b>) Host genes with expression profiles highly correlated with <i>HERV-W env</i> tag abundance (r<sup>2</sup>≥0.75) were analyzed using DAVID tools (<a href=\"http://david.abcc.ncifcrf.gov/\" target=\"_blank\">http://david.abcc.ncifcrf.gov/</a>) for enriched gene ontology (GO) terms. Genes related to transcriptional activity and regulations were strongly associated with HERV-W <i>env</i> expression. (ND = none detected).</p>", "links"=>[], "tags"=>["analyses"], "article_id"=>449254, "categories"=>["Virology", "Genetics", "Immunology", "Neuroscience"], "users"=>["Rakesh K. Bhat", "Kristofor K. Ellestad", "B. Matt Wheatley", "Rene Warren", "Robert A. Holt", "Christopher Power"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019176.g005", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HERV_W_env_sequence_analyses_in_healthy_brain_specimens_/449254", "title"=>"HERV-W <i>env</i> sequence analyses in healthy brain specimens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-29 02:34:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/778557"], "description"=>"<p>The human genome contains several endogenous retroviral envelope sequences similar to <i>ERVWE1</i>. (<b>A</b>) Chromosomal loci (arrows) depicting sequences similar to <i>ERVWE1 (accession No.</i> NM_014590). The genomic location of the <i>ERVWE1</i> locus on chromosome 7 is indicated with a box. (<b>B</b>) Phylogenetic analysis of HERV-W <i>env</i> gene at 12 different putative gene loci; the dendrogram was constructed based on DNA sequence by the Neighbor-Joining method using the MEGA4 program. The tree is rooted to the MSRV prototype <i>env</i> sequence, which was used as an out-group gene sequence. (<b>C</b>) Amplification and cloning of the 650 bp region of HERV-W <i>env</i> gene: (<b>i</b>) ethidium bromide-stained agarose gel showing HERV-W <i>env</i> gene amplicons JEG and BeWo cell lines, (<b>ii</b>) frequency of HERV-W <i>env</i> cDNA sequences cloned from human fetal astrocytes (HFA), neurons (HFN), microglia (HFM) and immortalized cell lines. In primary cells, HERV-W <i>env</i> sequences were derived from the 7q21.2 (ERVWE1) locus as well as other loci, while all HERV-W <i>env</i> sequences from immortalized cell lines appeared to be encoded by 7q21.2. The values in parenthesis indicate percent diversity among clones for each patient relative to ERVWE1. (ND = none detected).</p>", "links"=>[], "tags"=>["genetics and genomics", "Virology", "immunology", "neurological disorders"], "article_id"=>448925, "categories"=>["Virology", "Genetics", "Immunology", "Neuroscience"], "users"=>["Rakesh K. Bhat", "Kristofor K. Ellestad", "B. Matt Wheatley", "Rene Warren", "Robert A. Holt", "Christopher Power"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019176.g001", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HERV_W_env_sequence_mapping_and_detection_/448925", "title"=>"HERV-W <i>env</i> sequence mapping and detection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-29 02:28:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/778812"], "description"=>"<p>(<b>A</b>) Deep sequencing revealed HERV-W and related -<i>env</i>, -<i>LTR</i> and -<i>pol</i> RNA tags in fetal and adult samples, although the frequency of <i>env</i> tags was highest in all specimens. (<b>B</b>) Transcript levels of HERV-W <i>env</i> gene normalized to GAPDH, were highest in fetal brain samples. (<b>C</b>) Western blot analysis disclosed up-regulation of Syncytin-1 immunoreactivity in fetal samples relative to β-actin expression.</p>", "links"=>[], "tags"=>["rna", "syncytin-1", "abundance", "fetal"], "article_id"=>449177, "categories"=>["Virology", "Genetics", "Immunology", "Neuroscience"], "users"=>["Rakesh K. Bhat", "Kristofor K. Ellestad", "B. Matt Wheatley", "Rene Warren", "Robert A. Holt", "Christopher Power"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019176.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HERV_W_env_RNA_and_Syncytin_1_abundance_in_healthy_human_fetal_and_adult_brain_samples_/449177", "title"=>"HERV-W <i>env</i> RNA and Syncytin-1 abundance in healthy human fetal and adult brain samples.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-29 02:32:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/778724"], "description"=>"<p>(<b>A</b>) Chromosomal loci encoding HERV-W <i>env</i> sequences in MS and non-MS samples showed 7q21.2 was the predominant locus in MS and non-MS samples, while placental clones were derived from multiple chromosomal locations. Values in parenthesis indicate percent diversity among clones for each patient relative to ERVWE1. (<b>B</b>) Phylogenetic analysis of HERV-W <i>env</i> sequences from MS and non-MS samples, based on DNA sequence by the neighbor-joining method. The tree was rooted to MSRV prototype <i>env</i> sequence, which was used as an out-group gene sequence. (<b>C</b>) Correlation between sequence diversity within samples with respect to ERVWE1 and HERV-W <i>env</i> abundance in MS and non-MS samples. (ND = none detected).</p>", "links"=>[], "tags"=>["analyses", "autopsied"], "article_id"=>449093, "categories"=>["Virology", "Genetics", "Immunology", "Neuroscience"], "users"=>["Rakesh K. Bhat", "Kristofor K. Ellestad", "B. Matt Wheatley", "Rene Warren", "Robert A. Holt", "Christopher Power"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019176.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HERV_W_env_sequence_analyses_from_autopsied_brain_white_matter_/449093", "title"=>"HERV-W <i>env</i> sequence analyses from autopsied brain white matter.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-29 02:31:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/390720", "https://ndownloader.figshare.com/files/390841", "https://ndownloader.figshare.com/files/390890", "https://ndownloader.figshare.com/files/390965"], "description"=>"<div><h3>Background</h3><p>The glycoprotein, Syncytin-1, is encoded by a human endogenous retrovirus (HERV)-W <em>env</em> gene and is capable of inducing neuroinflammation. The specific allele(s) responsible for Syncytin-1 expression in the brain is uncertain. Herein, HERV-W <em>env</em> diversity together with Syncytin-1 abundance and host immune gene profiles were examined in the nervous system using a multiplatform approach.</p> <h3>Results</h3><p>HERV-W <em>env</em> sequences were encoded by multiple chromosomal encoding loci in primary human neurons compared with less chromosomal diversity in astrocytes and microglia (<em>p</em><0.05). HERV-W <em>env</em> RNA sequences cloned from brains of patients with systemic or neurologic diseases were principally derived from chromosomal locus 7q21.2. Within the same specimens, HERV-W <em>env</em> transcript levels were correlated with the expression of multiple proinflammatory genes (<em>p</em><0.05). Deep sequencing of brain transcriptomes disclosed the <em>env</em> transcripts to be the most abundant HERV-W transcripts, showing greater expression in fetal compared with healthy adult brain specimens. Syncytin-1's expression in healthy brain specimens was derived from multiple encoding loci and linked to distinct immune and developmental gene profiles.</p> <h3>Conclusions</h3><p>Syncytin-1 expression in the brain during disease was associated with neuroinflammation and was principally encoded by a full length provirus. The present studies also highlighted the diversity in HERV gene expression within the brain and reinforce the potential contributions of HERV expression to neuroinflammatory diseases.</p> </div>", "links"=>[], "tags"=>["age-", "disease-dependent", "herv-w", "allelic", "neuroimmune"], "article_id"=>137183, "categories"=>["Cancer", "Genetics", "Immunology", "Neuroscience"], "users"=>["Rakesh K. Bhat", "Kristofor K. Ellestad", "B. Matt Wheatley", "Rene Warren", "Robert A. Holt", "Christopher Power"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0019176.s001", "https://dx.doi.org/10.1371/journal.pone.0019176.s002", "https://dx.doi.org/10.1371/journal.pone.0019176.s003", "https://dx.doi.org/10.1371/journal.pone.0019176.s004"], "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Age_and_Disease_Dependent_HERV_W_Envelope_Allelic_Variation_in_Brain_Association_with_Neuroimmune_Gene_Expression/137183", "title"=>"Age- and Disease-Dependent HERV-W Envelope Allelic Variation in Brain: Association with Neuroimmune Gene Expression", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-04-29 01:59:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/778657"], "description"=>"<p>(<b>A</b>) A heatmap showing relative expression of host immune genes relevant to neuroinflammation in MS and non-MS white matter samples, generated based on real time RT-PCR studies (* indicates statistically up- or down regulated genes). (<b>B</b>) Median HERV-W <i>env</i> transcript levels in non-MS and MS autopsied white matter specimens showing increased levels in MS brain-derived samples. (<b>C</b>) Regression analyses of host immune gene with HERV-W <i>env</i> transcript abundance. Transcripts expressed as relative fold change to the house keeping gene, GAPDH. (Spearman r; Mann-Whitney, <i>U</i> test, *<i>p</i><0.05, **<i>p</i><0.005, ***<i>p</i><0.0005).</p>", "links"=>[], "tags"=>["genetics and genomics", "Virology", "immunology", "neurological disorders"], "article_id"=>449023, "categories"=>["Virology", "Genetics", "Immunology", "Neuroscience"], "users"=>["Rakesh K. Bhat", "Kristofor K. Ellestad", "B. Matt Wheatley", "Rene Warren", "Robert A. Holt", "Christopher Power"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0019176.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HERV_W_env_and_immune_gene_expression_in_brain_white_matter_/449023", "title"=>"HERV-W <i>env</i> and immune gene expression in brain white matter.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-04-29 02:30:23"}

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Relative Metric

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