Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection
Identifieur interne : 000785 ( Pmc/Curation ); précédent : 000784; suivant : 000786Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection
Auteurs : Patrick Younan [États-Unis] ; Rodrigo I. Santos [États-Unis] ; Palaniappan Ramanathan [États-Unis] ; Mathieu Iampietro [États-Unis] ; Andrew Nishida [États-Unis] ; Mukta Dutta [États-Unis] ; Tatiana Ammosova [États-Unis] ; Michelle Meyer [États-Unis] ; Michael G. Katze [États-Unis] ; Vsevolod L. Popov [États-Unis] ; Sergei Nekhai [États-Unis] ; Alexander Bukreyev [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2019.
Abstract
Ebola virus (EBOV) infections are characterized by a pronounced lymphopenia that is highly correlative with fatalities. However, the mechanisms leading to T-cell depletion remain largely unknown. Here, we demonstrate that both viral mRNAs and antigens are detectable in CD4+ T cells despite the absence of productive infection. A protein phosphatase 1 inhibitor, 1E7-03, and siRNA-mediated suppression of viral antigens were used to demonstrate
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DOI: 10.1371/journal.ppat.1008068
PubMed: 31648236
PubMed Central: 6812753
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xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Dutta, Mukta" sort="Dutta, Mukta" uniqKey="Dutta M" first="Mukta" last="Dutta">Mukta Dutta</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Microbiology, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Ammosova, Tatiana" sort="Ammosova, Tatiana" uniqKey="Ammosova T" first="Tatiana" last="Ammosova">Tatiana Ammosova</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Department of Medicine, Howard University, Washington, D.C., United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Howard University, Washington, D.C.</wicri:regionArea></affiliation></author><author><name sortKey="Meyer, Michelle" sort="Meyer, Michelle" uniqKey="Meyer M" first="Michelle" last="Meyer">Michelle Meyer</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name><affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Department of Microbiology, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, University of Washington, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff005"><addr-line>National Primate Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>National Primate Research Center, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Popov, Vsevolod L" sort="Popov, Vsevolod L" uniqKey="Popov V" first="Vsevolod L." last="Popov">Vsevolod L. Popov</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Nekhai, Sergei" sort="Nekhai, Sergei" uniqKey="Nekhai S" first="Sergei" last="Nekhai">Sergei Nekhai</name><affiliation wicri:level="1"><nlm:aff id="aff004"><addr-line>Department of Medicine, Howard University, Washington, D.C., United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Howard University, Washington, D.C.</wicri:regionArea></affiliation></author><author><name sortKey="Bukreyev, Alexander" sort="Bukreyev, Alexander" uniqKey="Bukreyev A" first="Alexander" last="Bukreyev">Alexander Bukreyev</name><affiliation wicri:level="1"><nlm:aff id="aff001"><addr-line>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>Department Microbiology & Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department Microbiology & Immunology, the University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Ebola virus (EBOV) infections are characterized by a pronounced lymphopenia that is highly correlative with fatalities. However, the mechanisms leading to T-cell depletion remain largely unknown. Here, we demonstrate that both viral mRNAs and antigens are detectable in CD4<sup>+</sup> T cells despite the absence of productive infection. A protein phosphatase 1 inhibitor, 1E7-03, and siRNA-mediated suppression of viral antigens were used to demonstrate <italic>de novo</italic> synthesis of viral RNAs and antigens in CD4<sup>+</sup> T cells, respectively. Cell-to-cell fusion of permissive Huh7 cells with non-permissive Jurkat T cells impaired productive EBOV infection suggesting the presence of a cellular restriction factor. We determined that viral transcription is partially impaired in the fusion T cells. Lastly, we demonstrate that exposure of T cells to EBOV resulted in autophagy through activation of ER-stress related pathways. These data indicate that exposure of T cells to EBOV results in an abortive infection, which likely contributes to the lymphopenia observed during EBOV infections.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Henao Restrepo, Am" uniqKey="Henao Restrepo A">AM Henao-Restrepo</name></author><author><name sortKey="Camacho, A" uniqKey="Camacho A">A Camacho</name></author><author><name sortKey="Longini, Im" uniqKey="Longini I">IM Longini</name></author><author><name sortKey="Watson, Ch" uniqKey="Watson C">CH Watson</name></author><author><name sortKey="Edmunds, Wj" uniqKey="Edmunds W">WJ Edmunds</name></author><author><name sortKey="Egger, M" uniqKey="Egger M">M Egger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ledgerwood, Je" uniqKey="Ledgerwood J">JE Ledgerwood</name></author><author><name sortKey="Dezure, Ad" uniqKey="Dezure A">AD DeZure</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, CA USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31648236</article-id><article-id pub-id-type="pmc">6812753</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1008068</article-id><article-id pub-id-type="publisher-id">PPATHOGENS-D-19-00429</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cellular Types</subject><subj-group><subject>Animal Cells</subject><subj-group><subject>Blood Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>T Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cellular Types</subject><subj-group><subject>Animal Cells</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>T Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>T Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune Cells</subject><subj-group><subject>White Blood Cells</subject><subj-group><subject>T Cells</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Spectrum Analysis Techniques</subject><subj-group><subject>Spectrophotometry</subject><subj-group><subject>Cytophotometry</subject><subj-group><subject>Flow Cytometry</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cell Processes</subject><subj-group><subject>Cell Death</subject><subj-group><subject>Autophagic Cell Death</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject><subj-group><subject>Specimen Preparation and Treatment</subject><subj-group><subject>Staining</subject><subj-group><subject>Cell Staining</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Immune Physiology</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Physiology</subject><subj-group><subject>Immune Physiology</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune System Proteins</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune System Proteins</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Immune System Proteins</subject><subj-group><subject>Antibodies</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Proteins</subject><subj-group><subject>Post-Translational Modification</subject><subj-group><subject>Phosphorylation</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject><subj-group><subject>Cell Biology</subject><subj-group><subject>Cell Physiology</subject><subj-group><subject>Cell Fusion</subject></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v3"><subject>Biology and life sciences</subject><subj-group><subject>Biochemistry</subject><subj-group><subject>Nucleic acids</subject><subj-group><subject>RNA</subject><subj-group><subject>Guide RNA</subject></subj-group></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection</article-title><alt-title alt-title-type="running-head">Abortive Infection of Ebola virus in T-Lymphocytes</alt-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Younan</surname><given-names>Patrick</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Data curation</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Writing – original draft</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-2548-1288</contrib-id><name><surname>Santos</surname><given-names>Rodrigo I.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author" equal-contrib="yes"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-8121-7647</contrib-id><name><surname>Ramanathan</surname><given-names>Palaniappan</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Iampietro</surname><given-names>Mathieu</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nishida</surname><given-names>Andrew</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dutta</surname><given-names>Mukta</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff003"><sup>3</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0001-8777-1032</contrib-id><name><surname>Ammosova</surname><given-names>Tatiana</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Meyer</surname><given-names>Michelle</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Katze</surname><given-names>Michael G.</given-names></name><role content-type="http://credit.casrai.org/">Supervision</role><xref ref-type="aff" rid="aff003"><sup>3</sup></xref><xref ref-type="aff" rid="aff005"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Popov</surname><given-names>Vsevolod L.</given-names></name><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0003-0744-7887</contrib-id><name><surname>Nekhai</surname><given-names>Sergei</given-names></name><role content-type="http://credit.casrai.org/">Resources</role><xref ref-type="aff" rid="aff004"><sup>4</sup></xref></contrib><contrib contrib-type="author"><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-0342-4824</contrib-id><name><surname>Bukreyev</surname><given-names>Alexander</given-names></name><role content-type="http://credit.casrai.org/">Conceptualization</role><role content-type="http://credit.casrai.org/">Formal analysis</role><role content-type="http://credit.casrai.org/">Funding acquisition</role><role content-type="http://credit.casrai.org/">Investigation</role><role content-type="http://credit.casrai.org/">Methodology</role><role content-type="http://credit.casrai.org/">Project administration</role><role content-type="http://credit.casrai.org/">Supervision</role><role content-type="http://credit.casrai.org/">Writing – review & editing</role><xref ref-type="aff" rid="aff001"><sup>1</sup></xref><xref ref-type="aff" rid="aff002"><sup>2</sup></xref><xref ref-type="aff" rid="aff006"><sup>6</sup></xref><xref ref-type="corresp" rid="cor001">*</xref></contrib></contrib-group><aff id="aff001"><label>1</label><addr-line>Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></aff><aff id="aff002"><label>2</label><addr-line>Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></aff><aff id="aff003"><label>3</label><addr-line>Department of Microbiology, University of Washington, Seattle, Washington, United States of America</addr-line></aff><aff id="aff004"><label>4</label><addr-line>Department of Medicine, Howard University, Washington, D.C., United States of America</addr-line></aff><aff id="aff005"><label>5</label><addr-line>National Primate Research Center, Seattle, Washington, United States of America</addr-line></aff><aff id="aff006"><label>6</label><addr-line>Department Microbiology & Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Kawaoka</surname><given-names>Yoshihiro</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Wisconsin-Madison, UNITED STATES</addr-line></aff><author-notes><fn fn-type="COI-statement" id="coi001"><p>The authors have declared that no competing interests exist.</p></fn><corresp id="cor001">* E-mail: <email>alexander.bukreyev@utmb.edu</email></corresp></author-notes><pub-date pub-type="epub"><day>24</day><month>10</month><year>2019</year></pub-date><pub-date pub-type="collection"><month>10</month><year>2019</year></pub-date><volume>15</volume><issue>10</issue><elocation-id>e1008068</elocation-id><history><date date-type="received"><day>6</day><month>3</month><year>2019</year></date><date date-type="accepted"><day>3</day><month>9</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 Younan et al</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Younan et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><self-uri content-type="pdf" xlink:href="ppat.1008068.pdf"></self-uri><abstract><p>Ebola virus (EBOV) infections are characterized by a pronounced lymphopenia that is highly correlative with fatalities. However, the mechanisms leading to T-cell depletion remain largely unknown. Here, we demonstrate that both viral mRNAs and antigens are detectable in CD4<sup>+</sup> T cells despite the absence of productive infection. A protein phosphatase 1 inhibitor, 1E7-03, and siRNA-mediated suppression of viral antigens were used to demonstrate <italic>de novo</italic> synthesis of viral RNAs and antigens in CD4<sup>+</sup> T cells, respectively. Cell-to-cell fusion of permissive Huh7 cells with non-permissive Jurkat T cells impaired productive EBOV infection suggesting the presence of a cellular restriction factor. We determined that viral transcription is partially impaired in the fusion T cells. Lastly, we demonstrate that exposure of T cells to EBOV resulted in autophagy through activation of ER-stress related pathways. These data indicate that exposure of T cells to EBOV results in an abortive infection, which likely contributes to the lymphopenia observed during EBOV infections.</p></abstract><abstract abstract-type="summary"><title>Author summary</title><p>Lymphopenia is a common characteristic of the disease caused by EBOV. We determined that despite the apparent lack of productive infection, EBOV is capable of entering T cells and producing both viral RNAs and proteins. Furthermore, we demonstrate that EBOV causes an abortive infection in T cells due to the presence of a cellular restriction factor. The abortive infection was associated with cell death following ER-stress induced autophagy. Collectively, these findings suggest that abortive infection in T cells is likely to contribute to lymphopenia during Ebola virus disease, which is uniformly linked with the severity of the disease. All EBOV vaccine candidates utilize GP as the sole antigen inducing a protective antibody response and in some clinical trials were shown to induce adverse side effects. The present study suggests that these effects can be associated with GP, which may lead to abortive infection of the vaccine construct in T cells contributing to the inflammatory response to the vaccines.</p></abstract><funding-group><award-group id="award001"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000060</institution-id><institution>National Institute of Allergy and Infectious Diseases</institution></institution-wrap></funding-source><award-id>U19 AI109945-01</award-id><principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-0342-4824</contrib-id><name><surname>Bukreyev</surname><given-names>Alexander</given-names></name></principal-award-recipient></award-group><award-group id="award002"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000060</institution-id><institution>National Institute of Allergy and Infectious Diseases</institution></institution-wrap></funding-source><award-id>1R01AI102887-01A1</award-id><principal-award-recipient><contrib-id authenticated="true" contrib-id-type="orcid">http://orcid.org/0000-0002-0342-4824</contrib-id><name><surname>Bukreyev</surname><given-names>Alexander</given-names></name></principal-award-recipient></award-group><award-group id="award003"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100000052</institution-id><institution>NIH Office of the Director</institution></institution-wrap></funding-source><award-id>P51OD010425</award-id><principal-award-recipient><name><surname>Katze</surname><given-names>Michael G.</given-names></name></principal-award-recipient></award-group><funding-statement>This study was supported by the NIH grant U19 AI109945-01 Project 2 Molecular Basis for Ebola Virus Immune Paralysis (A.B.) and NIH grant 1R01AI102887-01A1 (A.B.). Sound Genomics, a service center of the Washington National Primate Research Center performed the mRNA sequencing and is supported by funds from the National Institutes of Health, the Office of the Director (Grant P51OD010425). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><fig-count count="6"></fig-count><table-count count="0"></table-count><page-count count="25"></page-count></counts><custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name><meta-value>All relevant data are within the manuscript and its Supporting Information files.</meta-value></custom-meta></custom-meta-group></article-meta><notes><title>Data Availability</title><p>All relevant data are within the manuscript and its Supporting Information files.</p></notes></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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