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...

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Bibliographic Details
Published in:PLoS pathogens 2019-10, Vol.15 (10), p.e1008068-e1008068
Main Authors: 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
Format: Article
Language:English
Subjects:
Animals
Antigens
Antigens, Viral - biosynthesis
Antigens, Viral - genetics
Apoptosis
Autophagy
Autophagy - physiology
Biology and Life Sciences
Care and treatment
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - virology
Cell activation
Cell death
Cell fusion
Cell Line
Chlorocebus aethiops
Cytokines
Dendritic cells
Depletion
Ebola hemorrhagic fever
Ebola virus
Ebolavirus
Ebolavirus - immunology
Endoplasmic Reticulum Stress - physiology
Epidemics
Exposure
Fatalities
Flow cytometry
Gene expression
Genomics
HEK293 Cells
Hemorrhagic Fever, Ebola - immunology
HIV
Host-Pathogen Interactions
Human immunodeficiency virus
Humans
Indoles - pharmacology
Infection
Infections
Investigations
Jurkat Cells
Kinases
Laboratories
Lymphocytes
Lymphocytes T
Lymphocytopenia
Lymphopenia
Lymphopenia - immunology
Medicine and Health Sciences
Messenger RNA
Pathology
Phagocytosis
Phosphatases
Phosphoprotein phosphatase
Protein phosphatase
Protein Phosphatase 1 - antagonists & inhibitors
Research and Analysis Methods
Risk factors
RNA Interference
RNA, Small Interfering - genetics
RNA, Viral - biosynthesis
RNA, Viral - genetics
siRNA
T cell receptors
T cells
Transcription
Transcription Factors - metabolism
Urea - analogs & derivatives
Urea - pharmacology
Vero Cells
Viral antigens
Viral infections
Viral Proteins - metabolism
Virus Replication - physiology
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1008068