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

PLoS Pathog. 2019 Oct 24;15(10):e1008068. doi: 10.1371/journal.ppat.1008068. eCollection 2019 Oct.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Viral / biosynthesis
  • Antigens, Viral / genetics
  • Autophagy / physiology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Chlorocebus aethiops
  • Ebolavirus / immunology*
  • Endoplasmic Reticulum Stress / physiology
  • HEK293 Cells
  • Hemorrhagic Fever, Ebola / immunology*
  • Host-Pathogen Interactions
  • Humans
  • Indoles / pharmacology
  • Jurkat Cells
  • Lymphopenia / immunology*
  • Protein Phosphatase 1 / antagonists & inhibitors
  • RNA Interference
  • RNA, Small Interfering / genetics
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Transcription Factors / metabolism
  • Urea / analogs & derivatives
  • Urea / pharmacology
  • Vero Cells
  • Viral Proteins / metabolism
  • Virus Replication / physiology*

Substances

  • 1E7-03 compound
  • Antigens, Viral
  • Indoles
  • RNA, Small Interfering
  • RNA, Viral
  • Transcription Factors
  • VP30 protein, ebola virus
  • Viral Proteins
  • Urea
  • Protein Phosphatase 1