Background: Ebola virus (EBOV) mainly targets cells of the myeloid lineage; however, extensive death of T-cells takes place in lethal infections. We have previously shown that EBOV VP40 in extracellular vesicle (EVs) causes recipient cell death in immune cells.
Methods: Using VP40-producing cell lines, we analyzed donor cell cycle, EV biogenesis, and recipient immune cell viability. EV contents were characterized by mass spectrometry, cytokine array, and Western blot. BSL-4 facilities were utilized for wild-type Ebola virus infection studies.
Results: VP40 EVs induced cell death by apoptosis in recipient T-cells and monocytes. VP40- producing cells had accelerated cell cycling, which was tied to EV biogenesis, resulting in fewer but larger EVs. VP40 EVs were enriched in several cytokines, including IL-15, TGF-β1, and IFN-γ. Finally, EBOV-infected cell and animal EVs contained VP40, NP, and GP.
Conclusions: EBOV VP40 resulted in dysregulated cell cycle and EV biogenesis in donor cells. Packaging of cytokines and EBOV proteins into EVs from infected cells may be responsible for the decimation of immune cells during EBOV pathogenesis.