Similar articles

Abstract: The 2014 ebola outbreak in West Africa trig-gered a global crisis. Nine countries have reported more than 20000 infection cases in total and nearly 8000 lives have been lost. The actual death toll is likely much higher than this figure; the death rate is as high as 70%, considering confirmed cases. The ebola virus launches its destruction by shutting down the host’s innate and adaptive immune systems. The virus then replicates itself out of control and causes a cytokine storm in the host. Consequently, the host’s overdriven immune system attacks its own endothelial cells and this leads to multiple organ hemorrhagic damage, the host dies of septic shock finally. Under current circumstances where no specific interventions have shown effectiveness against the virus, our opinions are justified in applying a non-specific anti-viral approach during the incubation period of virus infection as an essential protection to put the host’s immune system into an alert state and henceforth to slow down the viral replication. When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host’s immune system to recover.

对抗埃博拉的非特异性策略--I型干扰素防护高危人群及间充质干细胞控制脓血症

[1]Ansari, A.A., 2014. Clinical features and pathobiology of Ebolavirus infection. J. Autoimmun., 55:1-9.

[2]Baize, S., Leroy, E.M., Georges-Courbot, M.C., et al., 1999. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat. Med., 5(4):423-426.

[3]Baize, S., Leroy, E.M., Georges, A.J., et al., 2002. Inflammatory responses in Ebola virus-infected patients. Clin. Exp. Immunol., 128(1):163-168.

[4]Baxter, A.G., 2000. Symptomless infection with Ebola virus. Lancet, 355(9222):2178-2179.

[5]Bray, M., Mahanty, S., 2003. Ebola hemorrhagic fever and septic shock. J. Infect. Dis., 188(11):1613-1617.

[6]Cao, L., Zhang, L., Tian, L., et al., 2011. Antivirus evaluation and clinical evaluation of recombinant human interferon α2b spray. Chin. Med. Biotechnol., 6(5):336-340 (in Chinese).

[7]Cárdenas, W.B., Loo, Y.M., Gale, M., et al., 2006. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling. J. Virol., 80(11):5168-5178.

[8]Fowler, R.A., Fletcher, T., Fischer, W.A., et al., 2014. Caring for critically ill patients with Ebola virus disease. Perspectives from West Africa. Am. J. Respir. Crit. Care Med., 190(7):733-737.

[9]Geisbert, T.W., Hensley, L.E., Gibb, T.R., et al., 2000. Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. Lab. Invest., 80(2):171-186.

[10]Hoenen, T., Groseth, A., Falzarano, D., et al., 2006. Ebola virus: unravelling pathogenesis to combat a deadly disease. Trends Mol. Med., 12(5):206-215.

[11]Ivashkiv, L.B., Donlin, L.T., 2014. Regulation of type I interferon responses. Nat. Rev. Immunol., 14(1):36-49.

[12]Jahrling, P.B., Geisbert, T.W., Geisbert, J.B., et al., 1999. Evaluation of immune globulin and recombinant interferon-α2b for treatment of experimental Ebola virus infections. J. Infect. Dis., 179(s1):S224-S234.

[13]Kebriaei, P., Isola, L., Bahceci, E., 2009. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol. Blood Marrow Transpl., 15(7):804-811.

[14]Ksiazek, T.G., Rollin, P.E., Williams, A.J., et al., 1999. Clinical virology of Ebola hemorrhagic fever (EHF): virus, virus antigen, and IgG and IgM antibody findings among EHF patients in Kikwit, Democratic Republic of the Congo, 1995. J. Infect. Dis., 179(S1):S177-S187.

[15]le Bon, A., Tough, D.F., 2002. Links between innate and adaptive immunity via type I interferon. Curr. Opin. Immunol., 14(4):432-436.

[16]Leroy, E.M., Baize, S., Volchkov, V.E., et al., 2000. Human asymptomatic Ebola infection and strong inflammatory response. Lancet, 355(9222):2210-2215.

[17]Leroy, E.M., Baize, S., Debre, P., et al., 2001. Early immune responses accompanying human asymptomatic Ebola infections. Clin. Exp. Immunol., 124(3):453-460.

[18]Misasi, J., Sullivan, N.J., 2014. Camouflage and misdirection: the full-on assault of Ebola virus disease. Cell, 159(3):477-486.

[19]Mohamadzadeh, M., Chen, L., Schmaljohn, A.L., 2007. How Ebola and Marburg viruses battle the immune system. Nat. Rev. Immunol., 7(7):556-567.

[20]Pedrazza, L., Lunardelli, A., Luft, C., et al., 2014. Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model. Inflamm. Res., 63(9):719-729.

[21]Plock, J.A., Schnider, J.T., Solari, M.G., et al., 2013. Perspectives on the use of mesenchymal stem cells in vascularized composite allotransplantation. Front. Immunol., 4:175.

[22]Schieffelin, J.S., Shaffer, J.G., Goba, A., et al., 2014. Clinical illness and outcomes in patients with Ebola in Sierra Leone. N. Engl. J. Med., 371(22):2092-2100.

[23]Smith, L.M., Hensley, L.E., Geisbert, T.W., et al., 2013. Interferon-β therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever. J. Infect. Dis., 208(2):310-318.

[24]Stolzing, A., Jones, E., McGonagle, D., et al., 2008. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech. Ageing Dev., 129(3):163-173.

[25]Sullivan, N., Yang, Z.Y., Nabel, G.J., 2003. Ebola virus pathogenesis: implications for vaccines and therapies. J. Virol., 77(18):9733-9737.

[26]Sun, L., Akiyama, K., Zhang, H., et al., 2009. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells, 27(6):1421-1432.

[27]Toledano, H., D’Alterio, C., Czech, B., 2012. The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche. Nature, 485(7400):605-610.

[28]Tyndall, A., Pistoia, V., 2009. Mesenchymal stem cells combat sepsis. Nat. Med., 15(1):18-20.

[29]Wang, Y., Chen, X., Cao, W., et al., 2014. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat. Immunol., 15(11):1009-1016.

[30]Wannemuehler, T.J., Manukyan, M.C., Brewster, B.D., et al., 2012. Advances in mesenchymal stem cell research in sepsis. J. Surg. Res., 173(1):113-126.

[31]Wauquier, N., Becquart, P., Padilla, C., et al., 2010. Human fatal Zaire Ebola virus infection is associated with an aberrant innate immunity and with massive lymphocyte apoptosis. PLoS Negl. Trop. Dis., 4(10):e837.

[32]Xu, W., Edwards, M.R., Borek, D.M., et al., 2014. Ebola virus VP24 targets a unique NLS binding site on karyopherin alpha 5 to selectively compete with nuclear import of phosphorylated STAT1. Cell Host Microbe, 16(2):187-200.

[33]Zhang, L., Wang, H., 2014. Forty years of the war against Ebola. J. Zhejiang Univ.-Sci. B (Biomed. & Biotechnol.), 15(9):761-765.