Full Text:   <2177>

Summary:  <2143>

CLC number: R183.7

On-line Access: 2015-01-05

Received: 2014-12-15

Revision Accepted: 2014-12-23

Crosschecked: 2014-12-16

Cited: 8

Clicked: 5165

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Lei ZHANG

http://orcid.org/0000-0002-0638-6042

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.1 P.1-9

http://doi.org/10.1631/jzus.B1400365


Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis


Author(s):  Lei Zhang, Hao Wang, Yi-qing Zhang

Affiliation(s):  Tianjin International Joint Academy of Biomedicine, Tianjin 300457, China; more

Corresponding email(s):   biotech@china.com

Key Words:  Ebola, Type I interferon, Mesenchymal stromal cell, Non-specific immune modulation


Share this article to: More |Next Article >>>

Lei Zhang, Hao Wang, Yi-qing Zhang. Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis[J]. Journal of Zhejiang University Science B, 2015, 16(1): 1-9.

@article{title="Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis",
author="Lei Zhang, Hao Wang, Yi-qing Zhang",
journal="Journal of Zhejiang University Science B",
volume="16",
number="1",
pages="1-9",
year="2015",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400365"
}

%0 Journal Article
%T Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis
%A Lei Zhang
%A Hao Wang
%A Yi-qing Zhang
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 1
%P 1-9
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400365

TY - JOUR
T1 - Against Ebola: type I interferon guard risk and mesenchymal stromal cell combat sepsis
A1 - Lei Zhang
A1 - Hao Wang
A1 - Yi-qing Zhang
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 1
SP - 1
EP - 9
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400365


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

概要:埃博拉病毒急性感染具有极高的致死率,其基本特征表现在机体的先天免疫与过继免疫反应被压制,病毒疯狂复制引发强烈的细胞因子风暴并攻击血管系统,大面积细胞凋亡导致脓血症和多脏器功能衰竭,病人最终因体温下降、血压过低休克致死。在缺乏特异性治疗药物干预的情况下,仍有一部分感染者会自然康复,说明埃博拉感染是一种自限性疾病,机体自身的免疫系统在非特异性治疗措施帮助下最终能够清除病毒。埃博拉病毒部分地阻断了I型干扰素的产生和抗病毒信号途径,但有证据表明I型干扰素仍能够在一定程度上抑制病毒复制,潜伏期内予以预防性注射I型干扰素可望大幅度降低感染者体内病毒负载;间充质干细胞具有强大及可塑性的免疫调节作用,能够压制细胞因子风暴,支持血管内皮细胞增殖,抑制细胞凋亡,具有向炎症组织趋化和参与修复的能力,对于埃博拉感染终末期患者采用间充质干细胞治疗有望显著降低死亡风险和后遗症的发生率。当前绝大多数常见的病毒性感染缺乏特异性治疗药物,在相当长一段时期内,非特异性治疗手段仍是对抗病毒性疾病的基本策略。

关键词:埃博拉;非特异性策略;I型干扰素;间充质干细胞

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[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.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

马祥乐<matianqi0314@foxmail.com>

2015-02-21 21:27:41

no comment

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2023 Journal of Zhejiang University-SCIENCE