Extracellular Vesicles and Ebola Virus: A New Mechanism of Immune Evasion

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2019 May 5

PMID 31052499

Citations 19

Authors

Michelle L Pleet

Catherine DeMarino

Spencer W Stonier

John M Dye

Steven Jacobson

M Javad Aman

Fatah Kashanchi

Affiliations

Soon will be listed here.

Abstract

Ebola virus (EBOV) disease can result in a range of symptoms anywhere from virtually asymptomatic to severe hemorrhagic fever during acute infection. Additionally, spans of asymptomatic persistence in recovering survivors is possible, during which transmission of the virus may occur. In acute infection, substantial cytokine storm and bystander lymphocyte apoptosis take place, resulting in uncontrolled, systemic inflammation in affected individuals. Recently, studies have demonstrated the presence of EBOV proteins VP40, glycoprotein (GP), and nucleoprotein (NP) packaged into extracellular vesicles (EVs) during infection. EVs containing EBOV proteins have been shown to induce apoptosis in recipient immune cells, as well as contain pro-inflammatory cytokines. In this manuscript, we review the current field of knowledge on EBOV EVs including the mechanisms of their biogenesis, their cargo and their effects in recipient cells. Furthermore, we discuss some of the effects that may be induced by EBOV EVs that have not yet been characterized and highlight the remaining questions and future directions.

Citing Articles

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References

Hakonarson H, Maskeri N, Carter C, Grunstein M . Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle. J Clin Invest. 1999; 103(7):1077-87. PMC: 408262. DOI: 10.1172/JCI5809. View

Baize S, Leroy E, Georges-Courbot M, Capron M, Debre P, Fisher-Hoch S . Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med. 1999; 5(4):423-6. DOI: 10.1038/7422. View

Santiago F, Clark E, Chong S, Molina C, Mozafari F, Mahieux R . Transcriptional up-regulation of the cyclin D2 gene and acquisition of new cyclin-dependent kinase partners in human T-cell leukemia virus type 1-infected cells. J Virol. 1999; 73(12):9917-27. PMC: 113041. DOI: 10.1128/JVI.73.12.9917-9927.1999. View

Otani T, Nakamura S, Toki M, Motoda R, Kurimoto M, Orita K . Identification of IFN-gamma-producing cells in IL-12/IL-18-treated mice. Cell Immunol. 2000; 198(2):111-9. DOI: 10.1006/cimm.1999.1589. View

Wei Y, Kita M, Shinmura K, Yan X, Fukuyama R, Fushiki S . Expression of IFN-gamma in cerebrovascular endothelial cells from aged mice. J Interferon Cytokine Res. 2000; 20(4):403-9. DOI: 10.1089/107999000312342. View

Leroy E, Baize S, Volchkov V, Fisher-Hoch S, Georges-Courbot M, Capron M . Human asymptomatic Ebola infection and strong inflammatory response. Lancet. 2000; 355(9222):2210-5. DOI: 10.1016/s0140-6736(00)02405-3. View

Timmins J, Scianimanico S, Schoehn G, Weissenhorn W . Vesicular release of ebola virus matrix protein VP40. Virology. 2001; 283(1):1-6. DOI: 10.1006/viro.2001.0860. View

Jasenosky L, Neumann G, Lukashevich I, Kawaoka Y . Ebola virus VP40-induced particle formation and association with the lipid bilayer. J Virol. 2001; 75(11):5205-14. PMC: 114926. DOI: 10.1128/JVI.75.11.5205-5214.2001. View

Garrus J, von Schwedler U, Pornillos O, Morham S, Zavitz K, Wang H . Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell. 2001; 107(1):55-65. DOI: 10.1016/s0092-8674(01)00506-2. View

10.

Zang T, Bieniasz P . HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nat Med. 2001; 7(12):1313-9. DOI: 10.1038/nm1201-1313. View

11.

Bavari S, Bosio C, Wiegand E, Ruthel G, Will A, Geisbert T . Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. J Exp Med. 2002; 195(5):593-602. PMC: 2193767. DOI: 10.1084/jem.20011500. View

12.

Timoshanko J, Holdsworth S, Kitching A, Tipping P . IFN-gamma production by intrinsic renal cells and bone marrow-derived cells is required for full expression of crescentic glomerulonephritis in mice. J Immunol. 2002; 168(8):4135-41. DOI: 10.4049/jimmunol.168.8.4135. View

13.

Noda T, Sagara H, Suzuki E, Takada A, Kida H, Kawaoka Y . Ebola virus VP40 drives the formation of virus-like filamentous particles along with GP. J Virol. 2002; 76(10):4855-65. PMC: 136157. DOI: 10.1128/jvi.76.10.4855-4865.2002. View

14.

Baize S, Leroy E, Georges A, Georges-Courbot M, Capron M, Bedjabaga I . Inflammatory responses in Ebola virus-infected patients. Clin Exp Immunol. 2002; 128(1):163-8. PMC: 1906357. DOI: 10.1046/j.1365-2249.2002.01800.x. View

15.

Savina A, Vidal M, Colombo M . The exosome pathway in K562 cells is regulated by Rab11. J Cell Sci. 2002; 115(Pt 12):2505-15. DOI: 10.1242/jcs.115.12.2505. View

16.

Huang Y, Xu L, Sun Y, Nabel G . The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein. Mol Cell. 2002; 10(2):307-16. DOI: 10.1016/s1097-2765(02)00588-9. View

17.

Jeffers S, Sanders D, Sanchez A . Covalent modifications of the ebola virus glycoprotein. J Virol. 2002; 76(24):12463-72. PMC: 136726. DOI: 10.1128/jvi.76.24.12463-12472.2002. View

18.

Licata J, Simpson-Holley M, Wright N, Han Z, Paragas J, Harty R . Overlapping motifs (PTAP and PPEY) within the Ebola virus VP40 protein function independently as late budding domains: involvement of host proteins TSG101 and VPS-4. J Virol. 2003; 77(3):1812-9. PMC: 140960. DOI: 10.1128/jvi.77.3.1812-1819.2003. View

19.

Timmins J, Schoehn G, Ricard-Blum S, Scianimanico S, Vernet T, Ruigrok R . Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4. J Mol Biol. 2003; 326(2):493-502. DOI: 10.1016/s0022-2836(02)01406-7. View

20.

Szekely Bjorndal A, Szekely L, Elgh F . Ebola virus infection inversely correlates with the overall expression levels of promyelocytic leukaemia (PML) protein in cultured cells. BMC Microbiol. 2003; 3:6. PMC: 154099. DOI: 10.1186/1471-2180-3-6. View