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系統識別號 U0026-0408201011500500
論文名稱(中文) 內生性annexin A1 增加單純疱疹病毒感染小鼠的死亡率
論文名稱(英文) Absence of annexin A1 decreases herpes simplex virus lethality in mice
校院名稱 成功大學
系所名稱(中) 微生物及免疫學研究所
系所名稱(英) Department of Microbiology & Immunology
學年度 98
學期 2
出版年 99
研究生(中文) 柯貞妤
研究生(英文) Jhen-Yu Ke
學號 s4697404
學位類別 碩士
語文別 英文
論文頁數 39頁
口試委員 指導教授-陳舜華
口試委員-劉校生
口試委員-張堯
中文關鍵字 單純疱疹病毒  細胞因子  Anx-A1 
英文關鍵字 HSV  cellular factor  Anx-A1 
學科別分類
中文摘要 單純疱疹病毒(HSV)有第一型(HSV-1)和第二型(HSV-2)兩種血清型。已知世界上大約百分之九十的成人曾經被HSV-1感染過。感染HSV-1或是HSV-2均能夠引起腦炎,並且單純疱疹病毒感染後所誘導的腦炎是病毒感染引起的疾病中最危險,而且最具威脅性,同時也是臨床上最常見的偶發致死性腦炎。然而,目前關於此病毒如何與細胞因子進行交互作用而達到調節疾病發展的了解有限。先前一篇研究利用反轉錄病毒載體將annexin A1 (Anx-A1)的基因去除後,發現缺乏此內生性的Anx-A1細胞株不易被單純疱疹第一型感染。至今仍沒有研究來探討Anx-A1在單純疱疹病毒腦炎所扮演的角色。因此,本篇我們利用Anx-A1基因剔除小鼠來探討Anx-A1在單純疱疹病毒所引起的疾病中所扮演的角色。實驗室先前的結果發現證實Anx-A1缺陷型的小鼠胚胎纖維母細胞比較不容易被單純疱疹病毒第一型所感染。在本篇論文中,我們發現在病毒感染後,細胞的Anx-A1總表現量以及外翻現象(externalization)會增加。Anx-A1 透過增加HSV-1結合(binding)到細胞的能力,進而增加小鼠胚胎纖維母細胞形成病毒斑(plaques)的數目。接著我們更進一步利用免疫共同沉澱實驗,證明了Anx-A1和HSV有交互作用。另一方面,在小鼠的腦炎模式中,我們發現感染單純疱疹第一型的Anx-A1缺陷公鼠的存活率明顯地比野生型公鼠高百分之七十五,並且在眼睛、三叉神經,以及腦的平均病毒量都顯著地低於野生型公鼠。相同地,感染單純疱疹第二型的Anx-A1缺陷母鼠的存活率明顯地比野生型母鼠高百分之五十六,並且在三叉神經以及腦的平均病毒量都顯著地低於野生型母鼠。綜合以上實驗結果,我們知道缺乏內生性的Anx-A1會降低單純疱疹病毒感染小鼠的死亡率。
英文摘要 There are two serotypes of herpes simplex virus (HSV), HSV-1 and -2. HSV-1 infects about 90% adult population in the world and can induce devastating diseases. Both HSV-1 and HSV-2 can induce encephalitis (HSE), which is the most common cause of sporadic, fatal encephalitis. Current understanding of how the virus interacts with cellular factors to regulate HSE is limited. It has been shown that rat intestine epithelial cells with the gene encoding annexin A1 (Anx-A1) disrupted by a retrovirus vector is resistant to HSV-1 infection. To date, there is no study investigating the roles of Anx-A1 in HSE. Our previous study confirmed that the embryonic fibroblasts cultured from Anx-A1- deficient (Anx-A1-/-) mice were resistant to HSV-1 infection. In the present study, Western blot analysis showed that Anx-A1 expression and externalization was increased after infection. Anx-A1 enhanced the number of plaques formed in mouse embryonic fibroblasts through increasing the binding of HSV-1 to the cells. Furthermore, co-immunoprecipitation assay showed that Anx-A1 interact with virus. In vivo results showed that the survival rate of male Anx-A1-/- mice infected with HSV-1 was significantly higher than that of male wild-type mice by 75%. The mean viral titers in the eyes, trigeminal ganglia, and brains of male Anx-A1-/- mice were significantly lower than those of male wild-type mice. Similarly, the survival rate of female Anx-A1-/- mice infected with HSV-2 was significantly higher than that of female wild-type mice by 56%. The mean viral titers in the eyes, trigeminal ganglia, and brains of female Anx-A1-/- mice were lower than those of female wild-type mice with significant differences found in the trigeminal ganglia and brains. Taken together, we show here that absence of Anx-A1 decreases HSV lethality in mice.
論文目次 Abstract in Chinese---------------------3
Abstract--------------------------------4
Acknowledgements------------------------6
Contents--------------------------------8
Figure list-----------------------------9
Introduction---------------------------10
Materials and methods------------------15
Results--------------------------------19
Discussion-----------------------------23
References-----------------------------26
Figures--------------------------------30
參考文獻 1.Azwa, A., and S. E. Barton. 2009. Aspects of herpes simplex virus: a clinical review. J Fam Plann Reprod Health Care 35:237-42.
2.Campadelli-Fiume, G., M. Amasio, E. Avitabile, A. Cerretani, C. Forghieri, T. Gianni, and L. Menotti. 2007. The multipartite system that mediates entry of herpes simplex virus into the cell. Rev Med Virol 17:313-26.
3.Chatterjee, B. E., S. Yona, G. Rosignoli, R. E. Young, S. Nourshargh, R. J. Flower, and M. Perretti. 2005. Annexin 1-deficient neutrophils exhibit enhanced transmigration in vivo and increased responsiveness in vitro. J Leukoc Biol 78:639-46.
4.Cheshenko, N., and B. C. Herold. 2002. Glycoprotein B plays a predominant role in mediating herpes simplex virus type 2 attachment and is required for entry and cell-to-cell spread. J Gen Virol 83:2247-55.
5.Croxtall, J. D., and R. J. Flower. 1992. Lipocortin 1 mediates dexamethasone-induced growth arrest of the A549 lung adenocarcinoma cell line. Proc Natl Acad Sci U S A 89:3571-5.
6.Derry, M. C., M. R. Sutherland, C. M. Restall, D. M. Waisman, and E. L. Pryzdial. 2007. Annexin 2-mediated enhancement of cytomegalovirus infection opposes inhibition by annexin 1 or annexin 5. J Gen Virol 88:19-27.
7.Elftman, M. D., J. T. Hunzeker, J. C. Mellinger, R. H. Bonneau, C. C. Norbury, and M. E. Truckenmiller. Stress-induced glucocorticoids at the earliest stages of herpes simplex virus-1 infection suppress subsequent antiviral immunity, implicating impaired dendritic cell function. J Immunol 184:1867-75.
8.Gerke, V., C. E. Creutz, and S. E. Moss. 2005. Annexins: linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol 6:449-61.
9.Gerke, V., and S. E. Moss. 2002. Annexins: from structure to function. Physiol Rev 82:331-71.
10.Hannon, R., J. D. Croxtall, S. J. Getting, F. Roviezzo, S. Yona, M. J. Paul-Clark, F. N. Gavins, M. Perretti, J. F. Morris, J. C. Buckingham, and R. J. Flower. 2003. Aberrant inflammation and resistance to glucocorticoids in annexin 1-/- mouse. FASEB J 17:253-5.
11.Heldwein, E. E., and C. Krummenacher. 2008. Entry of herpesviruses into mammalian cells. Cell Mol Life Sci 65:1653-68.
12.Herold, B. C., R. J. Visalli, N. Susmarski, C. R. Brandt, and P. G. Spear. 1994. Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. J Gen Virol 75 ( Pt 6):1211-22.
13.Herold, B. C., D. WuDunn, N. Soltys, and P. G. Spear. 1991. Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity. J Virol 65:1090-8.
14.Huang, R. T., B. Lichtenberg, and O. Rick. 1996. Involvement of annexin V in the entry of influenza viruses and role of phospholipids in infection. FEBS Lett 392:59-62.
15.Jamieson, A. M., S. Yu, C. H. Annicelli, and R. Medzhitov. Influenza virus-induced glucocorticoids compromise innate host defense against a secondary bacterial infection. Cell Host Microbe 7:103-14.
16.Katoh, N. 2000. Detection of annexins I and IV in bronchoalveolar lavage fluids from calves inoculated with bovine herpes virus-1. J Vet Med Sci 62:37-41.
17.Knotts, F. B., M. L. Cook, and J. G. Stevens. 1974. Pathogenesis of herpetic encephalitis in mice after ophthalmic inoculation. J Infect Dis 130:16-27.
18.Lim, L. H., and S. Pervaiz. 2007. Annexin 1: the new face of an old molecule. FASEB J 21:968-75.
19.McArthur, S., S. Yazid, H. Christian, R. Sirha, R. Flower, J. Buckingham, and E. Solito. 2009. Annexin A1 regulates hormone exocytosis through a mechanism involving actin reorganization. FASEB J 23:4000-10.
20.Nishiyama, Y. 1996. Herpesvirus genes: molecular basis of viral replication and pathogenicity. Nagoya J Med Sci 59:107-19.
21.Organ, E. L., J. Sheng, H. E. Ruley, and D. H. Rubin. 2004. Discovery of mammalian genes that participate in virus infection. BMC Cell Biol 5:41.
22.Parente, L., and E. Solito. 2004. Annexin 1: more than an anti-phospholipase protein. Inflamm Res 53:125-32.
23.Perretti, M., and R. J. Flower. 1996. Measurement of lipocortin 1 levels in murine peripheral blood leukocytes by flow cytometry: modulation by glucocorticoids and inflammation. Br J Pharmacol 118:605-10.
24.Pietropaolo, R. L., and T. Compton. 1997. Direct interaction between human cytomegalovirus glycoprotein B and cellular annexin II. J Virol 71:9803-7.
25.Pomeranz, L. E., A. E. Reynolds, and C. J. Hengartner. 2005. Molecular biology of pseudorabies virus: impact on neurovirology and veterinary medicine. Microbiol Mol Biol Rev 69:462-500.
26.Rajcani, J., and V. Durmanova. 2000. Early expression of herpes simplex virus (HSV) proteins and reactivation of latent infection. Folia Microbiol (Praha) 45:7-28.
27.Raynal, P., and H. B. Pollard. 1994. Annexins: the problem of assessing the biological role for a gene family of multifunctional calcium- and phospholipid-binding proteins. Biochim Biophys Acta 1197:63-93.
28.Raynor, C. M., J. F. Wright, D. M. Waisman, and E. L. Pryzdial. 1999. Annexin II enhances cytomegalovirus binding and fusion to phospholipid membranes. Biochemistry 38:5089-95.
29.Reske, A., G. Pollara, C. Krummenacher, B. M. Chain, and D. R. Katz. 2007. Understanding HSV-1 entry glycoproteins. Rev Med Virol 17:205-15.
30.Rhee, H. J., G. Y. Kim, J. W. Huh, S. W. Kim, and D. S. Na. 2000. Annexin I is a stress protein induced by heat, oxidative stress and a sulfhydryl-reactive agent. Eur J Biochem 267:3220-5.
31.Rosengarth, A., and H. Luecke. 2003. A calcium-driven conformational switch of the N-terminal and core domains of annexin A1. J Mol Biol 326:1317-25.
32.Shukla, D., and P. G. Spear. 2001. Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. J Clin Invest 108:503-10.
33.Siakallis, G., D. A. Spandidos, and G. Sourvinos. 2009. Herpesviridae and novel inhibitors. Antivir Ther 14:1051-64.
34.Smith, C. L. 2007. Mouse embryo fibroblast (MEF) feeder cell preparation.,In F. M. Ausubel (ed.), New York, New York, USA. Current protocols in molecular 28:21-23.
35.Solito, E., H. C. Christian, M. Festa, A. Mulla, T. Tierney, R. J. Flower, and J. C. Buckingham. 2006. Post-translational modification plays an essential role in the translocation of annexin A1 from the cytoplasm to the cell surface. FASEB J 20:1498-500.
36.Solito, E., S. McArthur, H. Christian, F. Gavins, J. C. Buckingham, and G. E. Gillies. 2008. Annexin A1 in the brain--undiscovered roles? Trends Pharmacol Sci 29:135-42.
37.Terasaka, Y., D. Miyazaki, K. Yakura, T. Haruki, and Y. Inoue. Induction of IL-6 in transcriptional networks in corneal epithelial cells after herpes simplex virus type 1 infection. Invest Ophthalmol Vis Sci 51:2441-9.
38.Traverso, V., J. F. Morris, R. J. Flower, and J. Buckingham. 1998. Lipocortin 1 (annexin 1) in patches associated with the membrane of a lung adenocarcinoma cell line and in the cell cytoplasm. J Cell Sci 111 ( Pt 10):1405-18.
39.Tyler, K. L. 2004. Update on herpes simplex encephalitis. Rev Neurol Dis 1:169-78.
40.Whitley, R. J., D. W. Kimberlin, and B. Roizman. 1998. Herpes simplex viruses. Clin Infect Dis 26:541-53; quiz 554-5.
41.Whitley, R. J., and B. Roizman. 2001. Herpes simplex virus infections. Lancet 357:1513-8.
42.Wright, J. F., A. Kurosky, E. L. Pryzdial, and S. Wasi. 1995. Host cellular annexin II is associated with cytomegalovirus particles isolated from cultured human fibroblasts. J Virol 69:4784-91.
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