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

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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

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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., Ammosova, T., Meyer, M., Katze, M. G., Popov, V. L., Nekhai, S., & 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