Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection

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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Article numbere1008068
JournalPLoS pathogens
Volume15
Issue number10
DOIs
StatePublished - Jan 1 2019

Fingerprint

Ebolavirus
Lymphocyte Depletion
Ebola Hemorrhagic Fever
T-Lymphocytes
Infection
Viral Antigens
Lymphopenia
Jurkat Cells
Cell Fusion
Autophagy
Viral RNA
Small Interfering RNA
Messenger RNA

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Younan, P., Santos, R. I., Ramanathan, P., Iampietro, M., Nishida, A., Dutta, M., ... Bukreyev, A. (2019). Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. PLoS pathogens, 15(10), [e1008068]. https://doi.org/10.1371/journal.ppat.1008068

Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. / Younan, Patrick; Santos, Rodrigo I.; Ramanathan, Palaniappan; Iampietro, Mathieu; Nishida, Andrew; Dutta, Mukta; Ammosova, Tatiana; Meyer, Michelle; Katze, Michael G.; Popov, Vsevolod L.; Nekhai, Sergei; Bukreyev, Alexander.

In: PLoS pathogens, Vol. 15, No. 10, e1008068, 01.01.2019.

Research output: Contribution to journalArticle

Younan, P, Santos, RI, Ramanathan, P, Iampietro, M, Nishida, A, Dutta, M, Ammosova, T, Meyer, M, Katze, MG, Popov, VL, Nekhai, S & Bukreyev, A 2019, 'Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection', PLoS pathogens, vol. 15, no. 10, e1008068. https://doi.org/10.1371/journal.ppat.1008068
Younan P, Santos RI, Ramanathan P, Iampietro M, Nishida A, Dutta M et al. Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. PLoS pathogens. 2019 Jan 1;15(10). e1008068. https://doi.org/10.1371/journal.ppat.1008068
Younan, Patrick ; Santos, Rodrigo I. ; Ramanathan, Palaniappan ; Iampietro, Mathieu ; Nishida, Andrew ; Dutta, Mukta ; Ammosova, Tatiana ; Meyer, Michelle ; Katze, Michael G. ; Popov, Vsevolod L. ; Nekhai, Sergei ; Bukreyev, Alexander. / Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. In: PLoS pathogens. 2019 ; Vol. 15, No. 10.
@article{60d840aa6f7448a291f16987bba29636,
title = "Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection",
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 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.",
author = "Patrick Younan and Santos, {Rodrigo I.} and Palaniappan Ramanathan and Mathieu Iampietro and Andrew Nishida and Mukta Dutta and Tatiana Ammosova and Michelle Meyer and Katze, {Michael G.} and Popov, {Vsevolod L.} and Sergei Nekhai and Alexander Bukreyev",
year = "2019",
month = "1",
day = "1",
doi = "10.1371/journal.ppat.1008068",
language = "English (US)",
volume = "15",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "10",

}

TY - JOUR

T1 - Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection

AU - Younan, Patrick

AU - Santos, Rodrigo I.

AU - Ramanathan, Palaniappan

AU - Iampietro, Mathieu

AU - Nishida, Andrew

AU - Dutta, Mukta

AU - Ammosova, Tatiana

AU - Meyer, Michelle

AU - Katze, Michael G.

AU - Popov, Vsevolod L.

AU - Nekhai, Sergei

AU - Bukreyev, Alexander

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85074076819&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85074076819&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1008068

DO - 10.1371/journal.ppat.1008068

M3 - Article

C2 - 31648236

AN - SCOPUS:85074076819

VL - 15

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 10

M1 - e1008068

ER -