Ebola Virus VP40 Modulates Cell Cycle and Biogenesis of Extracellular Vesicles.

The Journal of Infectious Diseases
Michelle L PleetFatah Kashanchi

Abstract

Ebola virus (EBOV) mainly targets myeloid cells; however, extensive death of T cells is often observed in lethal infections. We have previously shown that EBOV VP40 in exosomes causes recipient immune cell death. Using VP40-producing clones, we analyzed donor cell cycle, extracellular vesicle (EV) biogenesis, and recipient immune cell death. Transcription of cyclin D1 and nuclear localization of VP40 were examined via kinase and chromatin immunoprecipitation assays. Extracellular vesicle contents were characterized by mass spectrometry, cytokine array, and western blot. Biosafety level-4 facilities were used for wild-type Ebola virus infection studies. VP40 EVs induced apoptosis in recipient T cells and monocytes. VP40 clones were accelerated in growth due to cyclin D1 upregulation, and nuclear VP40 was found bound to the cyclin D1 promoter. Accelerated cell cycling was related to EV biogenesis, resulting in fewer but larger EVs. VP40 EV contents were enriched in ribonucleic acid-binding proteins and cytokines (interleukin-15, transforming growth factor-β1, and interferon-γ). Finally, EBOV-infected cell and animal EVs contained VP40, nucleoprotein, and glycoprotein. Nuclear VP40 upregulates cyclin D1 levels, resulting in dysreg...Continue Reading

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Citations

May 6, 2019·Viruses·Michelle L PleetFatah Kashanchi
Oct 18, 2019·Frontiers in Microbiology·Daniel O PintoFatah Kashanchi
May 1, 2020·Journal of Biomolecular Structure & Dynamics·Raied A BadierahElrashdy M Redwan
Nov 9, 2018·Frontiers in Cellular and Infection Microbiology·Michelle L PleetFatah Kashanchi
Jul 22, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Ke LiaoGuoku Hu
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Christos DogrammatzisMaria Kalamvoki
Oct 25, 2020·Viruses·Allen CaobiAndrea D Raymond
Feb 26, 2021·International Journal of Nanomedicine·Sangiliyandi GurunathanJin-Hoi Kim
Jun 1, 2021·Frontiers in Cellular and Infection Microbiology·Xiaonan JiaLingxiang Mao
May 21, 2021·International Journal of Biological Macromolecules·Mathavan MuthaiyanAmouda Venkatesan
Aug 29, 2021·Viruses·Sergio Montaner-TarbesHernando Del Portillo

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Methods Mentioned

BETA
transfection
electrophoresis
size exclusion fractionation
protein assay
immunoprecipitation
PCR
ChIP
density gradient fractionation
electron microscopy

Software Mentioned

Excel
ZetaView analysis
ZetaView
Proteome Discoverer
ZetaView Z - NTA ( Particle Metrix

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis