Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases
Identifieur interne : 000413 ( Pmc/Checkpoint ); précédent : 000412; suivant : 000414Enrichment 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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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">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></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></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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<front><journal-meta><journal-id journal-id-type="nlm-journal-id">101708905</journal-id><journal-id journal-id-type="pubmed-jr-id">46714</journal-id><journal-id journal-id-type="nlm-ta">J Emerg Dis Virol</journal-id><journal-id journal-id-type="iso-abbrev">J Emerg Dis Virol</journal-id><journal-title-group><journal-title>Journal of emerging diseases and virology</journal-title></journal-title-group><issn pub-type="epub">2473-1846</issn></journal-meta><article-meta><article-id pub-id-type="pmid">29202119</article-id><article-id pub-id-type="pmc">5707126</article-id><article-id pub-id-type="manuscript">NIHMS900501</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Enrichment of Retroviral Sequences in Brain Tissue from Patients with Severe Demyelinating Diseases</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kriesel</surname><given-names>JD</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bhetariya</surname><given-names>PJ</given-names></name><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>BK</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wilson</surname><given-names>T</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Fischer</surname><given-names>KF</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib></contrib-group><aff id="A1"><label>1</label>Department of Internal Medicine, Division of Infectious Diseases, USA</aff><aff id="A2"><label>2</label>Yale University, Department of Ecology and Evolutionary Biology, New Haven, Connecticut, USA</aff><aff id="A3"><label>3</label>Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA</aff><author-notes><corresp id="FN1"><label>*</label>Corresponding author: John D Kriesel, Department of Internal Medicine, Division of Infectious Diseases, USA, Tel: 801-585-7314; <email>john.kriesel@hsc.utah.edu</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>21</day><month>8</month><year>2017</year></pub-date><pub-date pub-type="epub"><day>16</day><month>7</month><year>2017</year></pub-date><pub-date pub-type="ppub"><month>8</month><year>2017</year></pub-date><pub-date pub-type="pmc-release"><day>29</day><month>11</month><year>2017</year></pub-date><volume>3</volume><issue>2</issue><elocation-id>10.16966/2473-1846.132</elocation-id><permissions><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><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. This is consistent with the concept of HERV activation as a part of the innate immune response.</p></sec></abstract><kwd-group><kwd>Deep sequencing</kwd><kwd>RNA-seq</kwd><kwd>Next generation sequencing</kwd><kwd>Endogenous retroviruses</kwd><kwd>HERV</kwd><kwd>Multiple sclerosis</kwd><kwd>Progressive MS</kwd></kwd-group></article-meta></front><floats-group><fig id="F1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Hit Rate Comparison of Frozen Brain Specimens.</p><p>RNA was extracted from 14 normal control, 14 demyelination (including 2 NMO), and 7 other neurologic disease (OND) cryopreserved brain specimens. cDNA libraries were prepared and deep sequencing was performed. High quality sequences were matched to the non-redundant viral database using Mega BLAST with a word size of 28 bp. Hits (matches to the database) were normalized for the total number of high quality reads in each specimen and log<sub>10</sub> transformed, providing a ‘Log Hit Rate.’ Sequences mapping to non-vertebrate viruses (phages, plant and insect viruses) and cloning vectors were removed. Viral taxa not significantly enriched in any of the samples (e.g. VZV, EBV, and <italic>Enteroviruses</italic>) are not shown.</p></caption><graphic xlink:href="nihms900501f1"></graphic></fig><fig id="F2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>Retroviral Domain Discrimination Analysis.</p><p>Sequencing hits (matches) to the RVGC database were binned into retroviral domains. Mean log<sub>2</sub> transformed and centered hit rates to the retroviral domain types in RVGC for the demyelination (MS), OND and normal control specimens. The results are clustered using Cluster 3.0 [<xref rid="R41" ref-type="bibr">41</xref>], showing distinctly different expression patterns in most demyelination, control and OND specimens.</p></caption><graphic xlink:href="nihms900501f2"></graphic></fig><table-wrap id="T1" position="float" orientation="landscape"><label>Table 1</label><caption><p>Characteristics of the sequenced frozen brain specimens.</p></caption><table frame="box" rules="all"><thead><tr><th align="left" valign="middle" rowspan="1" colspan="1">Group</th><th align="center" valign="middle" rowspan="1" colspan="1">Specimen</th><th align="center" valign="middle" rowspan="1" colspan="1">PMI</th><th align="center" valign="middle" rowspan="1" colspan="1">Age</th><th align="center" valign="middle" rowspan="1" colspan="1">Sex</th><th align="center" valign="middle" rowspan="1" colspan="1">Collection Year</th><th align="left" valign="middle" rowspan="1" colspan="1">Clinical History</th><th align="left" valign="middle" rowspan="1" colspan="1">Specimen Location</th><th align="left" valign="middle" rowspan="1" colspan="1">Neuropathology Reading</th><th align="center" valign="middle" rowspan="1" colspan="1">HQ Reads</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="14" colspan="1"><bold>Normal Control</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">202</td><td align="center" valign="middle" rowspan="1" colspan="1">4</td><td align="center" valign="middle" rowspan="1" colspan="1">57</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1983</td><td align="left" valign="middle" rowspan="1" colspan="1">Post-surgical infection</td><td align="left" valign="middle" rowspan="1" colspan="1">cerebrum</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">91.5</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">214</td><td align="center" valign="middle" rowspan="1" colspan="1">4</td><td align="center" valign="middle" rowspan="1" colspan="1">56</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1981</td><td align="left" valign="middle" rowspan="1" colspan="1">Heart Disease</td><td align="left" valign="middle" rowspan="1" colspan="1">cerebrum</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">94.7</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3276</td><td align="center" valign="middle" rowspan="1" colspan="1">19</td><td align="center" valign="middle" rowspan="1" colspan="1">54</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2002</td><td align="left" valign="middle" rowspan="1" colspan="1">Heart Disease</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">93.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">33</td><td align="center" valign="middle" rowspan="1" colspan="1">5</td><td align="center" valign="middle" rowspan="1" colspan="1">69</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1983</td><td align="left" valign="middle" rowspan="1" colspan="1">Lung Disease</td><td align="left" valign="middle" rowspan="1" colspan="1">cerebrum</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">89.1</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3371</td><td align="center" valign="middle" rowspan="1" colspan="1">16</td><td align="center" valign="middle" rowspan="1" colspan="1">52</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2002</td><td align="left" valign="middle" rowspan="1" colspan="1">Lung Cancer</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">96.8</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3406</td><td align="center" valign="middle" rowspan="1" colspan="1">20</td><td align="center" valign="middle" rowspan="1" colspan="1">72</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2002</td><td align="left" valign="middle" rowspan="1" colspan="1">Heart Failure</td><td align="left" valign="middle" rowspan="1" colspan="1">temporal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">89.3</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3465</td><td align="center" valign="middle" rowspan="1" colspan="1">20</td><td align="center" valign="middle" rowspan="1" colspan="1">93</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2002</td><td align="left" valign="middle" rowspan="1" colspan="1">Bleeding</td><td align="left" valign="middle" rowspan="1" colspan="1">temporal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">105.2</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3482</td><td align="center" valign="middle" rowspan="1" colspan="1">14</td><td align="center" valign="middle" rowspan="1" colspan="1">79</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">Heart Disease</td><td align="left" valign="middle" rowspan="1" colspan="1">temporal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">97.5</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3543</td><td align="center" valign="middle" rowspan="1" colspan="1">12</td><td align="center" valign="middle" rowspan="1" colspan="1">73</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">Lung Disease</td><td align="left" valign="middle" rowspan="1" colspan="1">parietal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">105.2</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3348</td><td align="center" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">76</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2002</td><td align="left" valign="middle" rowspan="1" colspan="1">Heart Disease, Diabetes</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">102.7</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3465</td><td align="center" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">76</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">Heart Failure</td><td align="left" valign="middle" rowspan="1" colspan="1">occipital WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">107.3</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3637</td><td align="center" valign="middle" rowspan="1" colspan="1">13</td><td align="center" valign="middle" rowspan="1" colspan="1">76</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">Pneumonia</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">102.5</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3641</td><td align="center" valign="middle" rowspan="1" colspan="1">20</td><td align="center" valign="middle" rowspan="1" colspan="1">76</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">Stomach and Liver Cancer</td><td align="left" valign="middle" rowspan="1" colspan="1">parietal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">85.3</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3698</td><td align="center" valign="middle" rowspan="1" colspan="1">17</td><td align="center" valign="middle" rowspan="1" colspan="1">84</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">Breast Cancer</td><td align="left" valign="middle" rowspan="1" colspan="1">temporal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">normal</td><td align="center" valign="middle" rowspan="1" colspan="1">90.3</td></tr><tr><td align="left" valign="middle" rowspan="14" colspan="1"><bold>Demyelination (Progressive MS and NMO)</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">168</td><td align="center" valign="middle" rowspan="1" colspan="1">3</td><td align="center" valign="middle" rowspan="1" colspan="1">37</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">1984</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">cerebrum</td><td align="left" valign="middle" rowspan="1" colspan="1">reactivated MS</td><td align="center" valign="middle" rowspan="1" colspan="1">89.7</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">2443</td><td align="center" valign="middle" rowspan="1" colspan="1">26</td><td align="center" valign="middle" rowspan="1" colspan="1">49</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">1997</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">lymphocytic cuffing</td><td align="center" valign="middle" rowspan="1" colspan="1">99</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">2485</td><td align="center" valign="middle" rowspan="1" colspan="1">9</td><td align="center" valign="middle" rowspan="1" colspan="1">69</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1997</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">active MS</td><td align="center" valign="middle" rowspan="1" colspan="1">63.3</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">2696</td><td align="center" valign="middle" rowspan="1" colspan="1">21</td><td align="center" valign="middle" rowspan="1" colspan="1">86</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">1998</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic MS plaque</td><td align="center" valign="middle" rowspan="1" colspan="1">130.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">2946</td><td align="center" valign="middle" rowspan="1" colspan="1">15</td><td align="center" valign="middle" rowspan="1" colspan="1">59</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1999</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic perivascular inflammation</td><td align="center" valign="middle" rowspan="1" colspan="1">88.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3161</td><td align="center" valign="middle" rowspan="1" colspan="1">20</td><td align="center" valign="middle" rowspan="1" colspan="1">51</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2001</td><td align="left" valign="middle" rowspan="1" colspan="1">Secondary Progressive MS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">active MS with lymphocytic cuffing</td><td align="center" valign="middle" rowspan="1" colspan="1">89.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3185</td><td align="center" valign="middle" rowspan="1" colspan="1">14</td><td align="center" valign="middle" rowspan="1" colspan="1">50</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2001</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic MSplaque</td><td align="center" valign="middle" rowspan="1" colspan="1">91.1</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3509</td><td align="center" valign="middle" rowspan="1" colspan="1">11</td><td align="center" valign="middle" rowspan="1" colspan="1">74</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic MS plaque</td><td align="center" valign="middle" rowspan="1" colspan="1">87.2</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3816</td><td align="center" valign="middle" rowspan="1" colspan="1">21</td><td align="center" valign="middle" rowspan="1" colspan="1">47</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2004</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">macrophages and lymphocytic cuffing</td><td align="center" valign="middle" rowspan="1" colspan="1">91</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3840</td><td align="center" valign="middle" rowspan="1" colspan="1">23</td><td align="center" valign="middle" rowspan="1" colspan="1">61</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2003</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">macrophages and lymphocytic cuffing</td><td align="center" valign="middle" rowspan="1" colspan="1">95</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">3931</td><td align="center" valign="middle" rowspan="1" colspan="1">10</td><td align="center" valign="middle" rowspan="1" colspan="1">74</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2004</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">periventricular WM</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic active disease</td><td align="center" valign="middle" rowspan="1" colspan="1">73.8</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">5149</td><td align="center" valign="middle" rowspan="1" colspan="1">8</td><td align="center" valign="middle" rowspan="1" colspan="1">48</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">2010</td><td align="left" valign="middle" rowspan="1" colspan="1">PPMS</td><td align="left" valign="middle" rowspan="1" colspan="1">frontal WM</td><td align="left" valign="middle" rowspan="1" colspan="1">active MS</td><td align="center" valign="middle" rowspan="1" colspan="1">66.4</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">108</td><td align="center" valign="middle" rowspan="1" colspan="1">2</td><td align="center" valign="middle" rowspan="1" colspan="1">56</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">1998</td><td align="left" valign="middle" rowspan="1" colspan="1">NMO</td><td align="left" valign="middle" rowspan="1" colspan="1">midbrain and pons</td><td align="left" valign="middle" rowspan="1" colspan="1">demyelination with necrosis</td><td align="center" valign="middle" rowspan="1" colspan="1">72.5</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">290</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="left" valign="middle" rowspan="1" colspan="1">NMO</td><td align="left" valign="middle" rowspan="1" colspan="1">corpus callosum</td><td align="left" valign="middle" rowspan="1" colspan="1">demyelination consistent with NMO</td><td align="center" valign="middle" rowspan="1" colspan="1">82.3</td></tr><tr><td align="left" valign="middle" rowspan="7" colspan="1"><bold>OND Control</bold></td><td align="center" valign="middle" rowspan="1" colspan="1">1418</td><td align="center" valign="middle" rowspan="1" colspan="1">5</td><td align="center" valign="middle" rowspan="1" colspan="1">68</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1988</td><td align="left" valign="middle" rowspan="1" colspan="1">MS-like illness<xref rid="TFN10" ref-type="table-fn">†</xref></td><td align="left" valign="middle" rowspan="1" colspan="1">Frontal cortex</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic encephalitis</td><td align="center" valign="middle" rowspan="1" colspan="1">76.8</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">4403<xref rid="TFN9" ref-type="table-fn">*</xref></td><td align="center" valign="middle" rowspan="1" colspan="1">18</td><td align="center" valign="middle" rowspan="1" colspan="1">77</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2006</td><td align="left" valign="middle" rowspan="1" colspan="1">HSV encephalitis, stroke</td><td align="left" valign="middle" rowspan="1" colspan="1">Frontal cortex</td><td align="left" valign="middle" rowspan="1" colspan="1">active encephalitis</td><td align="center" valign="middle" rowspan="1" colspan="1">99.5</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">4471</td><td align="center" valign="middle" rowspan="1" colspan="1">12</td><td align="center" valign="middle" rowspan="1" colspan="1">73</td><td align="center" valign="middle" rowspan="1" colspan="1">F</td><td align="center" valign="middle" rowspan="1" colspan="1">2007</td><td align="left" valign="middle" rowspan="1" colspan="1">Rasmussen’s encephalitis</td><td align="left" valign="middle" rowspan="1" colspan="1">Frontal cortex</td><td align="left" valign="middle" rowspan="1" colspan="1">gliosis without active inflammation</td><td align="center" valign="middle" rowspan="1" colspan="1">49.4</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">710<xref rid="TFN9" ref-type="table-fn">*</xref></td><td align="center" valign="middle" rowspan="1" colspan="1">8</td><td align="center" valign="middle" rowspan="1" colspan="1">58</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1983</td><td align="left" valign="middle" rowspan="1" colspan="1">HSV encephalitis, chronic lymphocytic leukemia</td><td align="left" valign="middle" rowspan="1" colspan="1">Frontal cortex</td><td align="left" valign="middle" rowspan="1" colspan="1">active encephalitis</td><td align="center" valign="middle" rowspan="1" colspan="1">50.1</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">924<xref rid="TFN9" ref-type="table-fn">*</xref></td><td align="center" valign="middle" rowspan="1" colspan="1">24</td><td align="center" valign="middle" rowspan="1" colspan="1">86</td><td align="center" valign="middle" rowspan="1" colspan="1">M</td><td align="center" valign="middle" rowspan="1" colspan="1">1985</td><td align="left" valign="middle" rowspan="1" colspan="1">HSV encephalitis</td><td align="left" valign="middle" rowspan="1" colspan="1">Frontal cortex</td><td align="left" valign="middle" rowspan="1" colspan="1">chronic encephalitis</td><td align="center" valign="middle" rowspan="1" colspan="1">67.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">coloradoA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="left" valign="middle" rowspan="1" colspan="1">SSPE (measles)</td><td align="left" valign="middle" rowspan="1" colspan="1">NA</td><td align="left" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">67.9</td></tr><tr><td align="center" valign="middle" rowspan="1" colspan="1">coloradoB</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">NA</td><td align="left" valign="middle" rowspan="1" colspan="1">SSPE (measles)</td><td align="left" valign="middle" rowspan="1" colspan="1">NA</td><td align="left" valign="middle" rowspan="1" colspan="1">NA</td><td align="center" valign="middle" rowspan="1" colspan="1">66.9</td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p>NA = information not available</p></fn><fn id="TFN2"><p>NMO = neuromyelitis optica</p></fn><fn id="TFN3"><p>OND = other neurologic disease</p></fn><fn id="TFN4"><p>PMI = post-mortem interval (hours)</p></fn><fn id="TFN5"><p>HQ reads = high quality reads (in millions)</p></fn><fn id="TFN6"><p>PPMS = primary progressive multiple sclerosis</p></fn><fn id="TFN7"><p>SSPE = subacute sclerosing panencephalitis (measles infection)</p></fn><fn id="TFN8"><p>WM = white matter</p></fn><fn id="TFN9"><label>*</label><p>previously diagnosed as HSV encephalitis</p></fn><fn id="TFN10"><label>†</label><p>MS not confirmed by pathology</p></fn></table-wrap-foot></table-wrap><table-wrap id="T2" position="float" orientation="landscape"><label>Table 2</label><caption><title>Specific Retroviral Genes Overexpressed in the Demyelination Group</title><p>Fifty bp reads were aligned to all annotated HERV sequence in NCBI/GenBank using the Bowtie2application with the default settings for end to end alignment. Mean expression levels (reads per million per kilobase, FPKM) are shown for the demyelination (progressive MS and NMO) groups. Reads were mapped either: 1) singly, to their best matching RVCG sequence (Best Alignment) or, 2) using every reported Bowtie2 alignment to the RVGC (Comprehensive Alignment). P-values and False Discovery Rates (FDR) are reported, along with the ratio of the mean hit rates between the experimental and control groups. Retroviral associations are per the annotation in the Gypsy 2.0 database.</p></caption><table frame="box" rules="all"><thead><tr><th align="left" valign="middle" rowspan="1" colspan="1">Method</th><th align="left" valign="middle" rowspan="1" colspan="1">Group</th><th align="center" valign="middle" rowspan="1" colspan="1">Gene</th><th align="center" valign="middle" rowspan="1" colspan="1">Expression 1</th><th align="center" valign="middle" rowspan="1" colspan="1">Ratio2</th><th align="center" valign="middle" rowspan="1" colspan="1">P-value</th><th align="center" valign="middle" rowspan="1" colspan="1">FDR (q) D:C3</th><th align="left" valign="middle" rowspan="1" colspan="1">Recognition Domain</th></tr></thead><tbody><tr><td align="left" valign="middle" rowspan="4" colspan="1"><bold>Best Alignment</bold></td><td align="left" valign="top" rowspan="1" colspan="1">Demyelination</td><td align="center" valign="top" rowspan="1" colspan="1">ENV-U3</td><td align="center" valign="top" rowspan="1" colspan="1">958</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.0001</td><td align="center" valign="top" rowspan="1" colspan="1">0.006</td><td align="left" valign="top" rowspan="1" colspan="1">K-HERV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">(N=14)</td><td align="center" valign="top" rowspan="1" colspan="1">RT-U105</td><td align="center" valign="top" rowspan="1" colspan="1">300</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.0001</td><td align="center" valign="top" rowspan="1" colspan="1">0.032</td><td align="left" valign="top" rowspan="1" colspan="1">MMTV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PPMS only</td><td align="center" valign="top" rowspan="1" colspan="1">ENV-U3</td><td align="center" valign="top" rowspan="1" colspan="1">952</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.0002</td><td align="center" valign="top" rowspan="1" colspan="1">0.017</td><td align="left" valign="top" rowspan="1" colspan="1">K-HERV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">(N=11)</td><td align="center" valign="top" rowspan="1" colspan="1">RT-U105</td><td align="center" valign="top" rowspan="1" colspan="1">311</td><td align="center" valign="top" rowspan="1" colspan="1">1.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.00005</td><td align="center" valign="top" rowspan="1" colspan="1">0.014</td><td align="left" valign="top" rowspan="1" colspan="1">MMTV</td></tr><tr><td align="left" valign="middle" rowspan="14" colspan="1"><bold>Comprehensive Alignment</bold></td><td align="left" valign="top" rowspan="1" colspan="1">Demyelination</td><td align="center" valign="top" rowspan="1" colspan="1">INT-U176</td><td align="center" valign="top" rowspan="1" colspan="1">775</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.0001</td><td align="center" valign="top" rowspan="1" colspan="1">0.036</td><td align="left" valign="top" rowspan="1" colspan="1">MuERV-L</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">(N=14)</td><td align="center" valign="top" rowspan="1" colspan="1">INT-U45</td><td align="center" valign="top" rowspan="1" colspan="1">94</td><td align="center" valign="top" rowspan="1" colspan="1">2.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.0003</td><td align="center" valign="top" rowspan="1" colspan="1">0.044</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">GAG-U21</td><td align="center" valign="top" rowspan="1" colspan="1">52</td><td align="center" valign="top" rowspan="1" colspan="1">2.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.0003</td><td align="center" valign="top" rowspan="1" colspan="1">0.009</td><td align="left" valign="top" rowspan="1" colspan="1">K-HERV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">GAG-U22</td><td align="center" valign="top" rowspan="1" colspan="1">43</td><td align="center" valign="top" rowspan="1" colspan="1">2.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.0011</td><td align="center" valign="top" rowspan="1" colspan="1">0.018</td><td align="left" valign="top" rowspan="1" colspan="1">HERV-K10</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">ENV-U59</td><td align="center" valign="top" rowspan="1" colspan="1">1540</td><td align="center" valign="top" rowspan="1" colspan="1">1.9</td><td align="center" valign="top" rowspan="1" colspan="1">0.0009</td><td align="center" valign="top" rowspan="1" colspan="1">0.037</td><td align="left" valign="top" rowspan="1" colspan="1">RTVL-Ia</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">ENV-U3</td><td align="center" valign="top" rowspan="1" colspan="1">960</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.00007</td><td align="center" valign="top" rowspan="1" colspan="1">0.006</td><td align="left" valign="top" rowspan="1" colspan="1">K-HERV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">KRAB-U15</td><td align="center" valign="top" rowspan="1" colspan="1">9880</td><td align="center" valign="top" rowspan="1" colspan="1">1.8</td><td align="center" valign="top" rowspan="1" colspan="1">0.001</td><td align="center" valign="top" rowspan="1" colspan="1">0.017</td><td align="left" valign="top" rowspan="1" colspan="1">KRAB</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">KRAB-U13</td><td align="center" valign="top" rowspan="1" colspan="1">1027</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.001</td><td align="center" valign="top" rowspan="1" colspan="1">0.017</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">KRAB-U9</td><td align="center" valign="top" rowspan="1" colspan="1">1982</td><td align="center" valign="top" rowspan="1" colspan="1">1.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.006</td><td align="center" valign="top" rowspan="1" colspan="1">0.037</td><td align="left" valign="top" rowspan="1" colspan="1"></td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">PPMS only</td><td align="center" valign="top" rowspan="1" colspan="1">ENV-U3</td><td align="center" valign="top" rowspan="1" colspan="1">952</td><td align="center" valign="top" rowspan="1" colspan="1">1.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.0002</td><td align="center" valign="top" rowspan="1" colspan="1">0.019</td><td align="left" valign="top" rowspan="1" colspan="1">K-HERV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">(N=11)</td><td align="center" valign="top" rowspan="1" colspan="1">ENV-U59</td><td align="center" valign="top" rowspan="1" colspan="1">1617</td><td align="center" valign="top" rowspan="1" colspan="1">2</td><td align="center" valign="top" rowspan="1" colspan="1">0.0009</td><td align="center" valign="top" rowspan="1" colspan="1">0.04</td><td align="left" valign="top" rowspan="1" colspan="1">RTVL-Ia</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">GAG-U21</td><td align="center" valign="top" rowspan="1" colspan="1">56</td><td align="center" valign="top" rowspan="1" colspan="1">2.7</td><td align="center" valign="top" rowspan="1" colspan="1">0.00009</td><td align="center" valign="top" rowspan="1" colspan="1">0.003</td><td align="left" valign="top" rowspan="1" colspan="1">K-HERV</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">GAG-U22</td><td align="center" valign="top" rowspan="1" colspan="1">47</td><td align="center" valign="top" rowspan="1" colspan="1">2.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.0006</td><td align="center" valign="top" rowspan="1" colspan="1">0.009</td><td align="left" valign="top" rowspan="1" colspan="1">HERV-K10</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1"></td><td align="center" valign="top" rowspan="1" colspan="1">GAG-U8</td><td align="center" valign="top" rowspan="1" colspan="1">242</td><td align="center" valign="top" rowspan="1" colspan="1">1.5</td><td align="center" valign="top" rowspan="1" colspan="1">0.004</td><td align="center" valign="top" rowspan="1" colspan="1">0.041</td><td align="left" valign="top" rowspan="1" colspan="1">HERV-E</td></tr></tbody></table><table-wrap-foot><fn id="TFN11"><label>1</label><p>Expression is described as FPKM (Fragments Per Kilobase of transcript per Million mapped reads) × 1000</p></fn><fn id="TFN12"><label>2</label><p>Ratio = mean expression in the Demyelination or PPMS group divided by mean expression in the Control group</p></fn><fn id="TFN13"><label>3</label><p>False Discovery Rate (FDR) q-values were calculated over each domain type separately (e.g. RT, ENV, GAG, etc.)</p></fn></table-wrap-foot></table-wrap></floats-group></pmc><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 Kriesel</name></noRegion><name sortKey="Bhetariya, Pj" sort="Bhetariya, Pj" uniqKey="Bhetariya P" first="Pj" last="Bhetariya">Pj Bhetariya</name><name sortKey="Chan, Bk" sort="Chan, Bk" uniqKey="Chan B" first="Bk" last="Chan">Bk Chan</name><name sortKey="Fischer, Kf" sort="Fischer, Kf" uniqKey="Fischer K" first="Kf" last="Fischer">Kf Fischer</name><name sortKey="Wilson, T" sort="Wilson, T" uniqKey="Wilson T" first="T" last="Wilson">T. 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