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

埃博拉病毒介导的 T 淋巴细胞耗竭是流产感染的结果

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作者: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

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.

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