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

• 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
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008068

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.