Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection.
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 absen...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008068 |
| _version_ | 1819029811498057728 |
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| author | Patrick Younan Rodrigo I Santos Palaniappan Ramanathan Mathieu Iampietro Andrew Nishida Mukta Dutta Tatiana Ammosova Michelle Meyer Michael G Katze Vsevolod L Popov Sergei Nekhai Alexander Bukreyev |
| author_facet | Patrick Younan Rodrigo I Santos Palaniappan Ramanathan Mathieu Iampietro Andrew Nishida Mukta Dutta Tatiana Ammosova Michelle Meyer Michael G Katze Vsevolod L Popov Sergei Nekhai Alexander Bukreyev |
| author_sort | Patrick Younan |
| collection | DOAJ |
| description | 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 de novo synthesis of viral RNAs and antigens in CD4+ 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. |
| first_indexed | 2024-12-21T06:20:11Z |
| format | Article |
| id | doaj.art-7ea5b7073c814c918c0555489bf6afc1 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T06:20:11Z |
| publishDate | 2019-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-7ea5b7073c814c918c0555489bf6afc12022-12-21T19:13:17ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-10-011510e100806810.1371/journal.ppat.1008068Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection.Patrick YounanRodrigo I SantosPalaniappan RamanathanMathieu IampietroAndrew NishidaMukta DuttaTatiana AmmosovaMichelle MeyerMichael G KatzeVsevolod L PopovSergei NekhaiAlexander BukreyevEbola 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 de novo synthesis of viral RNAs and antigens in CD4+ 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.https://doi.org/10.1371/journal.ppat.1008068 |
| spellingShingle | Patrick Younan Rodrigo I Santos Palaniappan Ramanathan Mathieu Iampietro Andrew Nishida Mukta Dutta Tatiana Ammosova Michelle Meyer Michael G Katze Vsevolod L Popov Sergei Nekhai Alexander Bukreyev Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. PLoS Pathogens |
| title | Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. |
| title_full | Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. |
| title_fullStr | Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. |
| title_full_unstemmed | Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. |
| title_short | Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. |
| title_sort | ebola virus mediated t lymphocyte depletion is the result of an abortive infection |
| url | https://doi.org/10.1371/journal.ppat.1008068 |
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