Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection
Identifieur interne : 000862 ( Main/Exploration ); précédent : 000861; suivant : 000863Ebola 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
Url:
DOI: 10.1371/journal.ppat.1008068
PubMed: 31648236
PubMed Central: 6812753
Affiliations:
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Santos</name><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Ramanathan, Palaniappan" sort="Ramanathan, Palaniappan" uniqKey="Ramanathan P" first="Palaniappan" last="Ramanathan">Palaniappan Ramanathan</name><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Iampietro, Mathieu" sort="Iampietro, Mathieu" uniqKey="Iampietro M" first="Mathieu" last="Iampietro">Mathieu Iampietro</name><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Nishida, Andrew" sort="Nishida, Andrew" uniqKey="Nishida A" first="Andrew" last="Nishida">Andrew Nishida</name><affiliation wicri:level="4"><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><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Dutta, Mukta" sort="Dutta, Mukta" uniqKey="Dutta M" first="Mukta" last="Dutta">Mukta Dutta</name><affiliation wicri:level="4"><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><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></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><wicri:noRegion>D.C.</wicri:noRegion></affiliation></author><author><name sortKey="Meyer, Michelle" sort="Meyer, Michelle" uniqKey="Meyer M" first="Michelle" last="Meyer">Michelle Meyer</name><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></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="4"><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><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Washington (État)</region></placeName></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="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></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><wicri:noRegion>D.C.</wicri:noRegion></affiliation></author><author><name sortKey="Bukreyev, Alexander" sort="Bukreyev, Alexander" uniqKey="Bukreyev A" first="Alexander" last="Bukreyev">Alexander Bukreyev</name><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><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><placeName><region type="state">Texas</region></placeName></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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Yang</name></author><author><name sortKey="Santiago, Ml" uniqKey="Santiago M">ML Santiago</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Callahan, Mk" uniqKey="Callahan M">MK Callahan</name></author><author><name sortKey="Popernack, Pm" uniqKey="Popernack P">PM Popernack</name></author><author><name sortKey="Tsutsui, S" uniqKey="Tsutsui S">S Tsutsui</name></author><author><name sortKey="Truong, L" uniqKey="Truong L">L Truong</name></author><author><name sortKey="Schlegel, Ra" uniqKey="Schlegel R">RA Schlegel</name></author><author><name sortKey="Henderson, Aj" uniqKey="Henderson A">AJ Henderson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gu, L" uniqKey="Gu L">L Gu</name></author><author><name sortKey="Sims, B" uniqKey="Sims B">B Sims</name></author><author><name sortKey="Krendelchtchikov, A" uniqKey="Krendelchtchikov A">A Krendelchtchikov</name></author><author><name sortKey="Tabengwa, E" uniqKey="Tabengwa 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sortKey="Erickson, Br" uniqKey="Erickson B">BR Erickson</name></author><author><name sortKey="Bawiec, Da" uniqKey="Bawiec D">DA Bawiec</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Flyak, Ai" uniqKey="Flyak A">AI Flyak</name></author><author><name sortKey="Ilinykh, Pa" uniqKey="Ilinykh P">PA Ilinykh</name></author><author><name sortKey="Murin, Cd" uniqKey="Murin C">CD Murin</name></author><author><name sortKey="Garron, T" uniqKey="Garron T">T Garron</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X Shen</name></author><author><name sortKey="Fusco, Ml" uniqKey="Fusco M">ML Fusco</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ilinykh, Pa" uniqKey="Ilinykh P">PA Ilinykh</name></author><author><name sortKey="Santos, Ri" uniqKey="Santos R">RI Santos</name></author><author><name sortKey="Gunn, Bm" uniqKey="Gunn B">BM Gunn</name></author><author><name sortKey="Kuzmina, Na" uniqKey="Kuzmina N">NA Kuzmina</name></author><author><name sortKey="Shen, X" uniqKey="Shen X">X Shen</name></author><author><name sortKey="Huang, K" uniqKey="Huang K">K Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kawakami, E" uniqKey="Kawakami E">E Kawakami</name></author><author><name sortKey="Watanabe, T" uniqKey="Watanabe T">T Watanabe</name></author><author><name sortKey="Fujii, K" uniqKey="Fujii K">K Fujii</name></author><author><name sortKey="Goto, H" uniqKey="Goto H">H Goto</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S Watanabe</name></author><author><name sortKey="Noda, T" uniqKey="Noda T">T Noda</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Afonina, I" uniqKey="Afonina I">I Afonina</name></author><author><name sortKey="Ankoudinova, I" uniqKey="Ankoudinova I">I Ankoudinova</name></author><author><name sortKey="Mills, A" uniqKey="Mills A">A Mills</name></author><author><name sortKey="Lokhov, S" uniqKey="Lokhov S">S Lokhov</name></author><author><name sortKey="Huynh, P" uniqKey="Huynh P">P Huynh</name></author><author><name sortKey="Mahoney, W" uniqKey="Mahoney W">W Mahoney</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thorvaldsdottir, H" uniqKey="Thorvaldsdottir H">H Thorvaldsdottir</name></author><author><name sortKey="Robinson, Jt" uniqKey="Robinson J">JT Robinson</name></author><author><name sortKey="Mesirov, Jp" uniqKey="Mesirov J">JP Mesirov</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Texas</li><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Texas"><name sortKey="Younan, Patrick" sort="Younan, Patrick" uniqKey="Younan P" first="Patrick" last="Younan">Patrick Younan</name></region><name sortKey="Ammosova, Tatiana" sort="Ammosova, Tatiana" uniqKey="Ammosova T" first="Tatiana" last="Ammosova">Tatiana Ammosova</name><name sortKey="Bukreyev, Alexander" sort="Bukreyev, Alexander" uniqKey="Bukreyev A" first="Alexander" last="Bukreyev">Alexander Bukreyev</name><name sortKey="Bukreyev, Alexander" sort="Bukreyev, Alexander" uniqKey="Bukreyev A" first="Alexander" last="Bukreyev">Alexander Bukreyev</name><name sortKey="Bukreyev, Alexander" sort="Bukreyev, Alexander" uniqKey="Bukreyev A" first="Alexander" last="Bukreyev">Alexander Bukreyev</name><name sortKey="Dutta, Mukta" sort="Dutta, Mukta" uniqKey="Dutta M" first="Mukta" last="Dutta">Mukta Dutta</name><name sortKey="Iampietro, Mathieu" sort="Iampietro, Mathieu" uniqKey="Iampietro M" first="Mathieu" last="Iampietro">Mathieu Iampietro</name><name sortKey="Iampietro, Mathieu" sort="Iampietro, Mathieu" uniqKey="Iampietro M" first="Mathieu" last="Iampietro">Mathieu Iampietro</name><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name><name sortKey="Katze, Michael G" sort="Katze, Michael G" uniqKey="Katze M" first="Michael G." last="Katze">Michael G. Katze</name><name sortKey="Meyer, Michelle" sort="Meyer, Michelle" uniqKey="Meyer M" first="Michelle" last="Meyer">Michelle Meyer</name><name sortKey="Meyer, Michelle" sort="Meyer, Michelle" uniqKey="Meyer M" first="Michelle" last="Meyer">Michelle Meyer</name><name sortKey="Nekhai, Sergei" sort="Nekhai, Sergei" uniqKey="Nekhai S" first="Sergei" last="Nekhai">Sergei Nekhai</name><name sortKey="Nishida, Andrew" sort="Nishida, Andrew" uniqKey="Nishida A" first="Andrew" last="Nishida">Andrew Nishida</name><name sortKey="Popov, Vsevolod L" sort="Popov, Vsevolod L" uniqKey="Popov V" first="Vsevolod L." last="Popov">Vsevolod L. Popov</name><name sortKey="Popov, Vsevolod L" sort="Popov, Vsevolod L" uniqKey="Popov V" first="Vsevolod L." last="Popov">Vsevolod L. Popov</name><name sortKey="Ramanathan, Palaniappan" sort="Ramanathan, Palaniappan" uniqKey="Ramanathan P" first="Palaniappan" last="Ramanathan">Palaniappan Ramanathan</name><name sortKey="Ramanathan, Palaniappan" sort="Ramanathan, Palaniappan" uniqKey="Ramanathan P" first="Palaniappan" last="Ramanathan">Palaniappan Ramanathan</name><name sortKey="Santos, Rodrigo I" sort="Santos, Rodrigo I" uniqKey="Santos R" first="Rodrigo I." last="Santos">Rodrigo I. Santos</name><name sortKey="Santos, Rodrigo I" sort="Santos, Rodrigo I" uniqKey="Santos R" first="Rodrigo I." last="Santos">Rodrigo I. Santos</name><name sortKey="Younan, Patrick" sort="Younan, Patrick" uniqKey="Younan P" first="Patrick" last="Younan">Patrick Younan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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