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

English version

Autoři: Patrick Younan ^aff001; Rodrigo I. Santos ^aff001; Palaniappan Ramanathan ^aff001; Mathieu Iampietro ^aff001; Andrew Nishida ^aff003; Mukta Dutta ^aff003; Tatiana Ammosova ^aff004; Michelle Meyer ^aff001; Michael G. Katze ^aff003; Vsevolod L. Popov ^aff001; Sergei Nekhai ^aff004; Alexander Bukreyev ^aff001
Působiště autorů: Department of Pathology, the University of Texas Medical Branch, Galveston, Texas, United States of America ^aff001; Galveston National Laboratory, the University of Texas Medical Branch, Galveston, Texas, United States of America ^aff002; Department of Microbiology, University of Washington, Seattle, Washington, United states of America ^aff003; Department of Medicine, Howard University, Washington, D.C., United States of America ^aff004; National Primate Research Center, Seattle, Washington, United States of America ^aff005; Department Microbiology & Immunology, the University of Texas Medical Branch, Galveston, Texas, United States of America ^aff006
Vyšlo v časopise: Ebola virus-mediated T-lymphocyte depletion is the result of an abortive infection. PLoS Pathog 15(10): e32767. doi:10.1371/journal.ppat.1008068
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008068

Souhrn

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.

Klíčová slova:

Antibodies – Autophagic cell death – Cell fusion – Cell staining – Flow cytometry – Guide RNA – Phosphorylation – T cells

Zdroje

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