Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases
Identifieur interne : 000F09 ( Main/Exploration ); précédent : 000F08; suivant : 000F10Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases
Auteurs : Jd Kriesel [États-Unis] ; Pj Bhetariya [États-Unis] ; Bk Chan [États-Unis] ; T. Wilson [États-Unis] ; Kf Fischer [États-Unis]Source :
- Journal of emerging diseases and virology [ 2473-1846 ] ; 2017.
Abstract
Our group has used deep sequencing to identify viral RNA signatures in human brain specimens. We have previously used this method to detect HSV1, GBV-C, and measles virus sequence in brain tissue from deceased donors. Deep sequencing was performed on brain specimens from a cohort of patients who died with progressive forms of MS, revealing evidence of increased expression of some human endogenous retrovirus (HERV) domains.
Identify RNA sequences and new antigens involved in the pathogenesis of MS
Deep sequencing was performed on RNA extracted from 12 progressive MS, 2 neuromyelitis optica (MS/NMO = demyelination group), 14 normal control, and 7 other neurologic disease (OND) control frozen brain specimens. The resulting single-ended 50 bp sequences (reads) were compared to a non redundant viral database representing (NRVDB) all 1.2 M viral records in GenBank. A retroviral gene catalog (RVGC) was prepared by identifying human genetic loci (GRCh37.p13) homologous to domains contained in the Gypsy 2.0 retro element database. Reads were aligned to the RVGC and human transcriptome with Bowtie2. The resulting viral hit rates (VHRs) were normalized by the number of high quality reads. The expression of human genes, including HERVs, was determined using Cufflinks. Comparisons between the groups were performed using the false discovery rate.
Fifty to 131 million high quality reads per specimen were obtained. Comparison of the reads to the NRVDB suggested that the demyelination and OND specimens had higher VHRs against some retroviral sequences compared with the controls. This was confirmed by retroviral domain averaging. Gene expression analysis showed differential expression among some HERV sequences. Single read mapping revealed one envelope and one reverse transcriptase sequence record that were significantly enriched among the demyelination samples compared to the normal controls. Less restrictive (comprehensive) read mapping showed that 2 integrase, 2 core, 2 envelope, and 3 KRAB sequences that were overexpressed in the demyelination group.
These data demonstrate that some endogenous retroviral sequences are significantly overexpressed in these demyelination brain tissue specimens, but the magnitude of this overexpression is small. This is consistent with the concept of HERV activation as a part of the innate immune response.
Url:
PubMed: 29202119
PubMed Central: 5707126
Affiliations:
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Wilson</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Fischer, Kf" sort="Fischer, Kf" uniqKey="Fischer K" first="Kf" last="Fischer">Kf Fischer</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">29202119</idno><idno type="pmc">5707126</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707126</idno><idno type="RBID">PMC:5707126</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000A57</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000A57</idno><idno type="wicri:Area/Pmc/Curation">000A57</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000A57</idno><idno type="wicri:Area/Pmc/Checkpoint">000413</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000413</idno><idno type="wicri:Area/Ncbi/Merge">000755</idno><idno type="wicri:Area/Ncbi/Curation">000755</idno><idno type="wicri:Area/Ncbi/Checkpoint">000755</idno><idno type="wicri:Area/Main/Merge">000F11</idno><idno type="wicri:Area/Main/Curation">000F09</idno><idno type="wicri:Area/Main/Exploration">000F09</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases</title><author><name sortKey="Kriesel, Jd" sort="Kriesel, Jd" uniqKey="Kriesel J" first="Jd" last="Kriesel">Jd Kriesel</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, Division of Infectious Diseases, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Division of Infectious Diseases</wicri:regionArea><wicri:noRegion>Division of Infectious Diseases</wicri:noRegion></affiliation></author><author><name sortKey="Bhetariya, Pj" sort="Bhetariya, Pj" uniqKey="Bhetariya P" first="Pj" last="Bhetariya">Pj Bhetariya</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Internal Medicine, Division of Infectious Diseases, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Internal Medicine, Division of Infectious Diseases</wicri:regionArea><wicri:noRegion>Division of Infectious Diseases</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Bk" sort="Chan, Bk" uniqKey="Chan B" first="Bk" last="Chan">Bk Chan</name><affiliation wicri:level="2"><nlm:aff id="A2">Yale University, Department of Ecology and Evolutionary Biology, New Haven, Connecticut, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Yale University, Department of Ecology and Evolutionary Biology, New Haven, Connecticut</wicri:regionArea><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Wilson, T" sort="Wilson, T" uniqKey="Wilson T" first="T" last="Wilson">T. Wilson</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author><author><name sortKey="Fischer, Kf" sort="Fischer, Kf" uniqKey="Fischer K" first="Kf" last="Fischer">Kf Fischer</name><affiliation wicri:level="2"><nlm:aff id="A3">Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah</wicri:regionArea><placeName><region type="state">Utah</region></placeName></affiliation></author></analytic><series><title level="j">Journal of emerging diseases and virology</title><idno type="eISSN">2473-1846</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Our group has used deep sequencing to identify viral RNA signatures in human brain specimens. We have previously used this method to detect HSV1, GBV-C, and measles virus sequence in brain tissue from deceased donors. Deep sequencing was performed on brain specimens from a cohort of patients who died with progressive forms of MS, revealing evidence of increased expression of some human endogenous retrovirus (HERV) domains.</p></sec><sec id="S2"><title>Objectives</title><p id="P2">Identify RNA sequences and new antigens involved in the pathogenesis of MS</p></sec><sec id="S3"><title>Methods</title><p id="P3">Deep sequencing was performed on RNA extracted from 12 progressive MS, 2 neuromyelitis optica (MS/NMO = demyelination group), 14 normal control, and 7 other neurologic disease (OND) control frozen brain specimens. The resulting single-ended 50 bp sequences (reads) were compared to a non redundant viral database representing (NRVDB) all 1.2 M viral records in GenBank. A retroviral gene catalog (RVGC) was prepared by identifying human genetic loci (GRCh37.p13) homologous to domains contained in the Gypsy 2.0 retro element database. Reads were aligned to the RVGC and human transcriptome with Bowtie2. The resulting viral hit rates (VHRs) were normalized by the number of high quality reads. The expression of human genes, including HERVs, was determined using Cufflinks. Comparisons between the groups were performed using the false discovery rate.</p></sec><sec id="S4"><title>Results</title><p id="P4">Fifty to 131 million high quality reads per specimen were obtained. Comparison of the reads to the NRVDB suggested that the demyelination and OND specimens had higher VHRs against some retroviral sequences compared with the controls. This was confirmed by retroviral domain averaging. Gene expression analysis showed differential expression among some HERV sequences. Single read mapping revealed one envelope and one reverse transcriptase sequence record that were significantly enriched among the demyelination samples compared to the normal controls. Less restrictive (comprehensive) read mapping showed that 2 integrase, 2 core, 2 envelope, and 3 KRAB sequences that were overexpressed in the demyelination group.</p></sec><sec id="S5"><title>Conclusions</title><p id="P5">These data demonstrate that some endogenous retroviral sequences are significantly overexpressed in these demyelination brain tissue specimens, but the magnitude of this overexpression is small. 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sortKey="Jones Brando, L" uniqKey="Jones Brando L">L Jones-Brando</name></author><author><name sortKey="Mallet, F" uniqKey="Mallet F">F Mallet</name></author><author><name sortKey="Yolken, Rh" uniqKey="Yolken R">RH Yolken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ruprecht, K" uniqKey="Ruprecht K">K Ruprecht</name></author><author><name sortKey="Obojes, K" uniqKey="Obojes K">K Obojes</name></author><author><name sortKey="Wengel, V" uniqKey="Wengel V">V Wengel</name></author><author><name sortKey="Gronen, F" uniqKey="Gronen F">F Gronen</name></author><author><name sortKey="Kim, Ks" uniqKey="Kim K">KS Kim</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Connecticut</li><li>Utah</li></region></list><tree><country name="États-Unis"><noRegion><name sortKey="Kriesel, Jd" sort="Kriesel, Jd" uniqKey="Kriesel J" first="Jd" last="Kriesel">Jd 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