臺灣博碩士論文加值系統

克沙奇病毒B3型屬於人類腸病毒B群 (human enterovirus B, HEV-B)，在臨床上能感染新生兒並引起心肌炎、肝炎、腦膜炎、胰臟炎、腦炎等疾病，其中克沙奇病毒B3型的抗體依賴性增強現象也已經在動物實驗中證實會增加肝炎的嚴重度。為探討克沙奇病毒B3型在肝細胞中的抗體依賴性增強現象，以及抗體依賴性增強的可能機制，我們分別利用老鼠肝細胞株 (AML12) 及人類肝細胞株 (Huh7) 建立克沙奇病毒B3型的抗體依賴性增強細胞 (in vitro) 感染模式。結果發現，當以克沙奇病毒B3型感染AML12細胞時，小鼠抗克沙奇病毒B3免疫球蛋白G (immunoglobulin G, IgG) 之抗體濃度為0.02-0.18 μg/ml時可以使病毒量增加。以克沙奇病毒B3型感染Huh7細胞時，當人類靜脈注射免疫球蛋白濃度介於約3-7 μg/ml時，病毒濃度會有增高的現象；當人類免疫球蛋白G抗體濃度介於0.012-2 μg/ml時，病毒濃度也會有增高的現象。利用阻斷試驗阻斷病毒受體克沙奇病毒-腺病毒受體 (coxsackievirus and Adenovirus Receptor, CAR) 以及衰變促進因子 (Decay Accelerating Factor, DAF/CD55) 後，分別進行病毒感染及抗體依賴性增強感染。結果顯示，克沙奇病毒B3型在AML12以及Huh7細胞中所引發的抗體依賴性增強現象需要克沙奇病毒-腺病毒受體的參與。此外，將Huh7細胞阻斷克沙奇病毒-腺病毒受體後進行病毒單獨感染，可以看到病毒濃度會隨著阻斷性抗體的濃度增加而降低，顯示克沙奇病毒-腺病毒受體在克沙奇病毒B3/2630的感染中扮演了重要的角色。若是將衰變促進因子進行阻斷，病毒濃度下降的情況則不明顯，但若是同時阻斷克沙奇病毒-腺病毒以及衰變促進因子，則會有些微的協同抑制作用。進一步偵測Huh7細胞在抗體依賴性增強感染下的細胞激素變化，結果發現在感染後0-10小時內細胞激素與對照組並無差異。此外，利用酵素切除人類免疫球蛋白G之Fc片段並加入病毒感染Huh7細胞，發現當抗體失去Fc片段後並不能引起抗體依賴性增強現象，顯示克沙奇病毒B3在肝細胞中的抗體依賴性增強現象是需要克沙奇病毒-腺病毒受體以及抗體 Fc 片段的參與，並且不是由抗體前端F(ab’)2片段所引起。另一方面，為探討是否有其他克沙奇病毒B型受體參與抗體依賴性增強機制之可能性，我們將過去文獻所發現可以作為克沙奇病毒B3型病毒受體之硫酸乙醯肝素 (Heparan sulfate) 視為可能的目標，以流式細胞儀偵測硫酸乙醯肝素在肝細胞的表現情形，並以肝素酶 (Heparinase) 移除細胞表面的硫酸乙醯肝素，以病毒感染後再以流式細胞儀分析病毒對細胞之感染率。結果發現當AML12細胞表面移除硫酸乙醯肝素後，克沙奇病毒之感染率相較於未移除硫酸乙醯肝素之AML12細胞並無明顯差異，因此暫排除硫酸乙醯肝素作為非經由克沙奇病毒腺病毒受體參與抗體依賴性增強機制之可能性。總結實驗結果，在小鼠肝細胞AML12以及人類肝細胞Huh7的細胞模式中，克沙奇病毒B3型確實可以在肝細胞引起抗體依賴性增強現象，此抗體依賴性增強現象是需要病毒受體克沙奇病毒-腺病毒受體，而非透過抗體前端F(ab’)2片段所引起。而在Huh7的細胞模式中，抗體依賴性增強感染在感染後10小時內並不會引起細胞激素分泌的變化。

Coxsackievirus B3 is a member of the human enterovirus B. CVB3 infection can cause a series of severe diseases in neonates such as myocarditis, hepatitis, meningitis and encephalitis. Antibody-dependent enhancement (ADE) of CVB3 infection has been shown to associate with disease severity in myocarditis. A hepatotropic CVB3 strain, CVB3/2630, can increase liver inflammation and damage through ADE mechanism, which was reported previously. Both coxsackievirus and adenovirus receptor (CAR) and Fcγ receptors (FcγRs) on immune cells are involved in the homologous ADE mechanisms of CVB3 infection. To study the role of CAR or FcγRs in ADE of CVB3 infection in hepatocytes, diluted mouse anti-CVB3 IgG, human intravenous immunoglobulin (IVIG) and anti-CVB3 IgG from human IVIG each infected with CVB3 directly to hepatocytes or hepatocytes pretreated with anti-CAR and anti-DAF antibodies were conducted. We found that diluted mouse anti-CVB3 IgG enhanced CVB3 infection at the concentration 0.02-0.18 μg/ml in AML12 (mouse hepatocytes); IVIG and anti-CVB3 IgG from IVIG enhanced CVB3 infection at the concentration 3-7 μg/ml and 0.012-2 μg/ml respectively in Huh7 (human hepatocytes). Blocking CAR on AML12 and Huh7 before infection, the viral titer showed no difference between with and without mouse anti-CVB3 IgG. In addition, the cytokines expression pattern did not change significantly after infection for 10 hours in Huh7 via ADE. On the other hand, blocking CAR on Huh7 before CVB3 infection resulted in a dose-dependent inhibition of viral titer, while blocking DAF didn’t inhibit viral titer obviously. However, blocking both CAR and DAF showed synergistic inhibition on viral titer. To further investigate the F(ab’)2 portion in ADE mechanisms of CVB3 in Huh7, we remove the Fc fragment from human IVIG and then infected Huh7 with CVB3 and F(ab’)2 fragment. The viral titer didn’t enhance as IgG lost its Fc fragment, which indicated the CAR-dependent ADE of CVB3 infection in Huh7 is not via F(ab’)2 fragment. As heparan sulfate is a CAR-independent mediator of the CVB3 infection, we hypothesized that heparan sulfate might participate the ADE. The expression level of heparan sulfate on AML12 and Huh7 was analyzed, then removed the heparan sulfate by heparinase I on AML12. Flow cytometry analysis showed that the infection rate of CVB3 on AML12 cells have no difference with heparan sulfate-free AML12 cells. Heparan sulfate may not involve in ADE of CVB3 infection in AML12. In conclusion, we demonstrated that CVB3 can induce ADE via CAR in hepatocyte, and the ADE of CVB3 infection is not through F(ab’)2 fragment or the involvement of heparan sulfate.

中文摘要 I
英文摘要 III
誌謝 V
目錄 VI
表目錄 X
圖目錄 XI
縮寫索引表 XII
壹、緒論 1
一、克沙奇病毒B型之介紹 1
A. 腸病毒之分類 1
B. 克沙奇病毒B型之病毒學概論 2
C. 克沙奇病毒B型之傳染途徑 5
D. 克沙奇病毒B型的流行病學 6
E. 克沙奇病毒B型與疾病 7
F. 克沙奇病毒B型與細胞發炎激素的關係 8
二、抗體依賴性增強與宿主免疫系統之相關性 11
A. 抗體依賴性增強機制 11
B. 相關的克沙奇病毒B型與其他病毒之抗體依賴性增強之研究 12
C. 抗體依賴性增強現象與疾病嚴重度之關連性 14
D. 抗體依賴性增強與宿主細胞激素的關連性 15
貳、研究動機與目的 16
參、實驗材料與方法 18
一、實驗材料 18
A、細胞株 18
B、病毒株 18
C、實驗動物 18
D、藥品與試劑 18
E、抗體 25
F、其他藥品與試劑 26
二、方法 28
A、細胞培養 28
B、病毒培養 29
C、抗體免疫球蛋白G (immunoglobulin G, IgG) 的製備與純化 31
D、以流式細胞儀偵測細胞表面之受體表現及病毒對細胞之感染率 33
E、抗體依賴性增強試驗與阻斷試驗 34
F. 細胞激素的測定 37
G. 肝素酶作用 (Heparinase treatment) 38
H. 統計分析方法與分析軟體 38
肆、結果 40
一、克沙奇病毒B3於小鼠肝細胞株 (AML12) 感染的抗體依賴性增強細胞 (in vitro) 感染模式 40
A. 克沙奇病毒B3的病毒量在次中和濃度之小鼠抗克沙奇病毒B3免疫球蛋白G存在下具有增加的現象 40
B. 克沙奇病毒-腺病毒受體 (CAR)、衰變促進因子 (DAF/CD55) 及Fcγ接受器與克沙奇病毒B3感染AML12細胞之抗體依賴性增強現象之相關性 41
二、克沙奇病毒B3於人類肝細胞株 (Huh7) 感染之抗體依賴性增強細胞 (in vitro) 模式 42
A. 以人類肝細胞株 (Huh7) 建立克沙奇病毒B3於不同濃度之人類靜脈注射免疫球蛋白存在下之細胞 (in vitro) 感染模式 42
B. 克沙奇病毒B3之病毒量於不同濃度之人類靜脈注射免疫球蛋白存在下具有增加的現象 42
C. 以人類肝細胞株 (Huh7) 建立克沙奇病毒B3在不同濃度之人類免疫球蛋白G存在下之細胞 (in vitro) 感染模式 43
D. 克沙奇病毒B3之病毒量在不同濃度人類免疫球蛋白G存在下具有增加的現象 43
E. 克沙奇病毒-腺病毒受體 (CAR)、衰變促進因子 (DAF/CD55) 及Fcγ接受器與克沙奇病毒B3感染Huh7 細胞之抗體依賴性增強現象之相關性 44
F. 同時阻斷克沙奇病毒-腺病毒受體 (CAR) 及衰變促進因子 (DAF/CD55) 對克沙奇B3於Huh7細胞之抗體依賴性增強現象之影響 46
G. Huh7細胞在克沙奇病毒B3之抗體依賴性增強現象中細胞激素的表現 48
H. 免疫球蛋白G 片段化對克沙奇病毒B3於Huh7細胞之抗體依賴性增強現象的影響 49
I. 硫酸乙醯肝素 (Heparan sulfate) 於克沙奇病毒B3感染肝細胞之角色 50
伍、討論 51
一、克沙奇病毒B3的抗體依賴性增強現象於流行病學之意義 51
二、克沙奇病毒B3於肝細胞之抗體依賴性增強現象與其他病毒之抗體依賴性增強現象比較 52
三、克沙奇病毒B3型之抗體依賴性增強細胞感染模式建立 53
四、受體阻斷試驗於克沙奇病毒B3型抗體依賴性增強現象之影響 54
五、Huh7細胞在克沙奇病毒B3之抗體依賴性增強現象中細胞激素的表現 56
六、免疫球蛋白G 片段化對克沙奇病毒B3於Huh7細胞之抗體依賴性增強現象的影響 56
七、硫酸乙醯肝素 (Heparan sulfate) 於克沙奇病毒B3感染肝細胞之角色 58
陸、結論 60
柒、參考文獻 61
表 71
圖 72
附錄 87
作者簡歷 95

Abzug, M. J. (2004) Presentation, diagnosis, and management of enterovirus infections in neonates. Paediatr Drugs. 6(1): 1-10.
Barth, H., Schafer, C., Adah, M. I., Zhang, F., Linhardt, R. J., Toyoda, H., Kinoshita-Toyoda, A., Toida, T., Van Kuppevelt, T. H., Depla, E., Von Weizsacker, F., Blum H. E., Baumert, T. F. (2003) Cellular binding of hepatitis C virus envelope glycoprotein E2 requires cell surface heparin sulfate. J Biol Chem. 278:41003-41012.
Bergelson, J. M., Mohanty, J. G., Crowell, R. L., John., N. F. ST., Lublin, D. M., Finberg, R. W. (1995) Coxsackievirus B3 adapted to growth in RD cells binds to decay-accelerating factor (CD55). J Virol. 69: 1903-1906.
Bergelson, J. M., Modlin, J. F., Wieland-Alter, W., Cunningham, J. A., Crowell, R. L., Finberg, R. W. (1997) Clinical Coxsackievirus B isolates differ from laboratory strains in their interaction with two cell surface receptors. J Infect Dis. 175: 697-700.
Bergelson, J. M., Cunningham, J. A., Droguett, G., Kurt-Jones, E. A., Krithivas, A., Hong, J. S., Horwitz, M. S., Crowell, R. L., Finberg, R. W. (1997) Isolation of a common receptor for coxsackie B viruses and adenoviruses 2 and 5. Science 275: 1320-1323.
Blumber, R. S., Koss, T., Story, C. M., Barisani, D., Polischuk, J., Lipin, A., Pablo, L., Green, R., Simister, N. E. (1995) A major histocompatibility complex class I-related Fc receptor for IgG on rat hepatocytes. J. Clin. Investig. 95: 2397-2402.
Bode, J. G., Albrecht, U., Häussinger, D., Heinrich, P., Schaper, F. (2012) Hepatic acute phase protein - regulation by IL-6-and IL-1-type cytokines involving STAT3 and its crosstalk with NF-κB-dependent signaling. Eur J Cell Biol. 91: 496-505.
Bradham, C. A., Plümpe, J., Manns, M. P., Brenner, D. A., Trautwein, C. (1998) Mechanisms of hepatic toxicity. I. TNF-induced liver injury. Am J Physiol. 275: G387-392.
Bryant, P. A., Tingay, D., Dargaville, P. A., Starr, M., Curtis, N. (2004) Neonatal coxsackie B virus infection—a treatable disease? Eur J Pediatr. 163: 223-228.
Cardosa, M. J., Porterfield, J. S., Gordon, S. (1983) Complement receptor mediates enhanced flavivirus replication in macrophages. J Exp Med. 158: 258–263.
Carson, S. D. (2001) Receptor for the group B coxsackieviruses and adenoviruses: CAR. Rev. Med. Virol. 11: 219-226.
Carter, J., Saunders, V. (2007) Virology – Priciples and Applications. John Wiley ＆ Sons, Ltd pp.157-172.
Chareonsirisuthigul, T., Kalayanarooj, S., Ubol, S. (2007) Dengue virus (DENV) antibody-dependent enhancement of infection upregulates the production of anti-inflammatory cytokines, but suppresses anti-DENV free radical and pro-infl ammatory cytokine production, in THP-1 cells. J Gen Virol. 88: 365–375.
Chehadeh, W., Lobert, P, Sauter, P., Goffard, A., Lucas, B., Weill, J., Vantyghem, M., Alm., G., Pigny, P., Hober, D. (2005) Viral protein VP4 is a target of human antibodies enhanceing coxsackievirus B4- and B3-induced synthesis of alpha interferon. J Virol. 79: 13882-13891.
Chen, Y., Maguire, T., Hileman, R. E., Fromm, J. R., Esko, J. D., Linhardt R. J., Marks, R. M. (1997) Dengue virus infectivity dependent on envelope protin binding of target cell heparan sulfate. Nat Med. 3: 866-871.
Coyne, C. B., Bergelson, J. M. (2006) Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell. 124: 119-131.
Feldman, S A., Audet, S., Beeler, J. A. (2000) The fusion glycoprotein of human respiratory syncytial virus facilitates virus attachment and infectivity via an interaction with cellular heparin sulfate. J Virol. 74: 6442-6447.
Faiweather, D., Yusung, S., Frisancho, S., Barrett, M., Gatewood, S., Steele, R., Rose, N. R. (2003) IL-12 receptor β1 and toll-like receptor 4 increase IL-1β-and IL-18-associated myocarditis and coxsackievirus replication. J Immunol. 170: 4731-4737.
Feuer, R., Pagarigan, R. R., Harkins, S., Liu, F., Hunzider, I. P., Whitton, J. L. (2005) Coxsackievirus targets proliferating neuronal progenitor cells in the neonatal CNS. J Neurosci. 25: 2434-2444.
Gauntt, C. J., Higdon, A. L., Arizpe, H. M., Tamayo, M. R., Crawley, R., Henkel, R. D., Pereira, M. E., Tracy, S. M., Cunningham, M. W. (1993) Epitopes shared between coxsackievirus B3 (CVB3) and normal heart tissue contribute to CVB3-induced murine myocarditis. Clin Immunol Immunopathol. 68: 129-134.
Gauntt, C. J., Arizpe, H. M., Higdon, A. L. Wood, J. J., Bowers, D. F., Rozek, M. M., Crawley, R. (1995) Molecular mimicry, anti-coxsackievirus B3 neutralizing monoclonal antibodies, and myocarditis. J Immunol. 154: 2983-2995.
Girn, J., Kavoosi, M., Chantler, J. (2002) Enhancement of coxsackievirus B3 infection by antibody to a different coxsackievirus strain. J Gen Virol. 83: 351-358.
Goodfellow, I. G., Sioofy, A. B, Powell, r. M., Evans, D. J. (2001) Echoviruses bind heparin sulfate at the cell surface. J Virol. 75: 4918-4921.
Halstead, S. B., O’Rourke, E. J., Allison, A. C. (1977) Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection. J Exp Med. 146: 218-229.
Halstead, S. B. (1981) The Alexander D. Langmuir Lecture. The pathogenesis of dengue. Molecular epidemiology in infectious disease. Am J Epidemiol. 114: 632-648.
Hober, D., Chehadeh, W., Bouzidi, A., Wattré, P. (2001) Antibody-dependent enhancement of coxsackievirus B4 infectivity of human peripheral blood mononuclear cells results in increased interferon-α synthesis. J Infect Dis. 184: 1098-1108.
Horwitz, M. S., Bradley, L. M., Harbertson, J., Krahl, T., Lee, J., Sarvennick, N. (1998) Diabetes induced by coxsackie virus: initiation by bystander damage and not molecular mimicry. Nat Med. 4: 781-785.
Huang, K. J., Yang, Y. C., Lin, Y. S., Huang, J. H., Liu, H. S., Yeh, T. M., Chen, S. H., Liu, C. C., Lei, H. Y. (2006) The dual-specific binding of dengue virus and target cells for the antibody-dependent enhancement of dengue virus infection. J Immunol. 176: 2825-2832.
Ilonen, I., Koivusalo, A. M., Höcherstedt, K., Isoniemi, H. (2006) Albumin dialysis has no clear effect on cytokine levels in patients with life-threatening liver insufficiency. Transplant Proc. 38: 3540-3543.
Jang, S. K., Krausslich, H. G., Nicklin, M. J., Duke, G. M., Palmenberg, A. C., Wimmer, E. (1988) A segment of the 5’ nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation. J Virol. 62:2636-2643.
Junghans, R. P., Anderson, C. L. (1996) The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor. Proc Natl Acad Sci USA. 93: 5512-5516.
Kalia, M., Chandra, V., Rahman, S. A., Sehgal, D., Jameel, S. (2009) Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protien and for viral infection. J Virol. 83: 12714-12724.
Kaplan, M. H., Klein, S. W., Mcphee, J., Harper, R. G. (1983) Group B coxsackievirus infections in infants younger than three months of age: a serious childhood illness. Rev Infect Dis. 5: 1019-1032.
Khetsuriani, N., Lamonte-Fowlkes, A., Oberst, S., Pallansch, M. A. (2006) Enterovirus surveillance - United States, 1970–2005. MMWR Surveill Summ. 55: 1–2.
Kishimoto, C., Kurokawa, M., Ochiai, H. (2002) Antiody-mediated immune enhancement in coxsackievirus B3 myocarditis. J Mol Cell Cardiol. 34: 1227-1238.
Klein, C., Wüstefeld, T., Assmus, U., Roskams, T., Rose-John, S., Müller, M., Manns, M. P., Ernst, M., Trautwein, C. (2005) The IL-6-gp130-STAT3 pathway in hepatocytes triggers liver protection in T cell-mediated liver injury. J. Clin. Invest. 115: 860-869.
Knowles, N. J. (2012) The picornavirus home page, http://www.picornaviridae.com/. Institute for Animal Health, Pirbright Laboratory, Pirbright, Woking, UK
Lidbury, B. A., Mahalingam, S. (2000) Specific ablation of antiviral gene expression in macrophages by antibody-dependent enhancement of Ross River virus infection. J Virol. 74: 8376–8381.
Lin, T. Y., Kao, H. T., Hsieh, S. H., Huang, Y. C., Chiu, C. H., Chou, Y. H., Yang, P. H., Lin, R, I., Tsao, K. C., Hsu, K. H., Chang, L. Y. (2003) Neonatal enterovirus infections: emphasis on risk factors of severe and fatal infections. Pediatr Infect Dis J. 22(10): 889-894.
Lindberg, A. M., Stalhandske, P. O. K., Pettersson, U. (1986) Genome of coxsackievirus B3. Virology. 156: 50-63.
Louis, H., Van Laethem, J. L., Wu, W., Quertinmont, E., Degraef, C., Van den Berg, K., Demols, A., Goldman, M., Le Moine, O., Geerts, A., Devière, J. (1998) Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 28: 1607-1615.
Mahalingam, S., Lidbury, B. A. (2002) Suppression of lipopolysaccharide induced antiviral transcription factor (STAT-1 and NFkB) complexes by antibody-dependent enhancement of macrophage infection by Ross River virus. Proc Natl Acad Sci USA. 99: 13819–13824.
Martino, T. A., Petric, M., Brown, M., Aitken, K., Gauntt, C. J., Richardson, C. D., Chow, L. H., Liu, P. P. (1998) Cardiovirulent coxsackieviruses and the decay-accelerating factor (CD55) receptor. Virology 244: 302-314.
McManus, B. M., Chow, L. H., Wilson, J. E., Anderson, D. R., Gulizia, J. M., Gauntt, C. J., Klingel, K. E., Beisel, K. W., Kandolf, R. (1993) Direct myocardial injury by enterovirus: a central role in the evolution of murine myocarditis. Clin Immunol Immunopathol. 68: 159-169.
Meyer, K., Ait-Goughoulte, M., Keck, Z. Y., Foung, S., Ray, R. (2008) Antibody-dependent enhancement of hepatitis C virus infection. J Virol. 82: 2140-2149.
Ouellet, A., Sherlock, R., Toye, B. Fung, K. F. K. (2004) Antenatal diagnosis of intrauterine infection with coxsackievirus B3 associated with live birth. Infect Dis Obstet Gynecol. 12: 23-26.
Palmer, P., Charley, B., Rombaut, B., Daëron, M., Lebon, P. (2000) Antibody-dependent induction of type-I interferons by poliovirus in human mononuclear blood cells requires the type II Fcγ receptor (CD32). Virology 278: 86-94.
Peiris, J. S., Porterfield, J. S. (1979) Antibody-mediated enhancement of flavivirus replication in macrophage-likecell lines. Nature 282: 509–511.
Peiris, J. S., Gordon, S., Unkeless, J. C., Porterfield, J. S. (1981) Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages. Nature 289: 189–191.
Pelletier, J., Sonenberg, N. (1988) Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334:320-325.
Reagan, K. J., Goldberg, B., Crowell, R. L. (1984) Altered receptor specificity of coxsackievirus B3 after growth in rhabdomyosarcoma cells. J Virol. 49: 635-640.
Rowell, D.L., Eckmann, L., Dwinell, B. M., Carpenter, S. P., Raucy, J. L., Yang, S. K., Kagnoff, M. F. (1997) Human hepatocytes express an array of proinflammatory cytokines after agonist stimulation or bacterial invasion. Am J Physiol. 273: G322-332.
Sauter, P., Hober, D. (2009) Mechanisms and results of the antibody-dependent enhancement of viral infections and role in the pathogenesis of coxsackievirus B-induced diseases. Microbes Infect. 11: 443-451.
Selinka, H. C., Wolde, A., Sauter, M., Kandolf, R., Klingel, K. (2004) Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism. Med Microbiol Immunol. 193: 127-131.
Schilling, R., Ijaz, S., Davidoff, M., Lee, J. Y., Locarnini, S., Williams, R., Naoumov, N. V. (2003) Endocytosis of hepatitis B immune globulin into hepatocytes inhibits the secretion of hepatitis B virus surface antigen and virions. J Virol. 77: 8882-8892.
Schneider-Schaulies, J. (2000) Cellular receptors for viruses: links to tropism and pathogenesis. J Gen Virol. 81: 1413-1429.
Schmidtke, M., Glück, B., Merkle, I., Hofmann, P., Stelzner, A., Gemsa, D. (2000) Cytokine profiles in heart, spleen, and thymus during the acute stage of experimental coxsackievirus B3-induced chronic myocarditis. J Med Virol. 61: 518-526.
Shafren, D. R., Bates, R., Agrez, M. V., Herd, R. L., Burns, G. F., Barry, R. D. (1995) Coxsackieviruses B1, B3, and B5 use decay accelerating factor as a receptor for cell attachment. J Virol. 69: 3873-3877.
Shafren, D. R., Williams, D.T., Barry, R. D. (1997) A decay-accelerating factor-binding strain of coxsackievirus B3 requires the coxsackievirus-adenovirus receptor protein to mediate lytic infection of rhabdomyosarcoma cells. J virol. 71: 9844-9848.
Streetz, K. L., Luedde, T., Manns, M. P., Trautwein, C. Interleukin 6 and liver regeneration. Gut. 47: 309-312.
Sullivan, N., Sun, Y., Binley, J., Lee, J., Barbas, C. F. 3rd, Parren, P. W., Burton, D. R., Sodroski, J. (1998) Determinants of human immunodeficiency virus type 1 envelope glycoprotein activation by soluble CD4 and monoclonal antibodies. J Virol. 72: 6332–6338.
Takada, A., Feldmann, H., Ksiazek, T. G., Kawaoka, Y. (2003) Antibody-dependent enhancement of Ebola virus infection. J Virol. 77: 7539–7544.
Takada, A., Kawaoka, Y. (2003) Antibody-dependent enhancement of viral infection: molecular mechanisms and invivo implications. Rev Med Virol. 13: 387-398.
Tebruegge, M., Curtis, N. (2009) Enterovirus infections in neonates. Semin Fetal Neonatal Med. 14: 222-227.
Tracy, S., Oberste, M. S., Drescher, K. M. (2008) Group B coxsackieviruses. Current Topics in Microbiology and Immunology. 323: p.90-99.
Tseng, F. C., Huang, H. C., Chi, C. Y., Lin, T. L., Liu, C. C., Jian, J. W., Hsu, L. C., Wu, H. S., Yang, J. Y., Chang, Y. W., Wang, H. C., Hsu, Y. W., Su, I. J. Wang, J. R. (2007) Epidemiological survey of enterovirus infections occurring in Taiwan between 2000-2005: analysis of sentinel physician surveillance data. J Med Virol. 79: 1850-1860.
Ubol, S., Phuklia, W., Kalayanarooj, S., Modhiran, N. (2010) Mechanisms of immune evasion induced by a complex of dengue virus and preexisting enhancing antibodies. J Infect Dis. 201: 923–935.
Vuorinen, T., Vainionpää, R., Vanharanta, R., Hyypiä, T. (1996) Susceptibility of human bone marrow cells and hematopoietic cell lines to coxsackievirus B3 infection. J Virol. 70: 9018-9023.
Wang, S. M., Chen, I. C., Su, L. Y., Huang, K. J., Lei, H. Y., Liu, C. C. (2010) Enterovirus 71 infection of monocytes with antibody-dependent enhancement. Clin Vaccine Immunol. 17: 1517-1523.
Wang, S. M., Liu, C. C., Yang, Y. J., Yang, H. B., Lin, C. H., Wang, J. R. (1998) Fatal coxsackievirus B infection in early infancy characterized by fulminant hepatitis. J Infect. 37: 270-273.
Whitton, J. L., Cornell, C. T., Feuer, R. (2005) Host and virus determinants of picornavirus pathogenesis and tropism. Nat Rev Mivrobiol. 3: 765-776.
Wu, J. C., Merlino, G., Fausto, N. (1994) Establishment and characterization of differentiated, nontransformed hepatocyte cell lines derived from mice transgenic for transforming growth factor alpha. Proc Natl Acad Sci USA. 91(2): 674-678.
Yasukawa, H., Yajima, T., Duplain, H., Iwatate, M., Kido, M., Hoshijima, M., Weitzman, M. D., Nakamura, T., Woodard, S., Xiong, D., Yochimura, A., Chien, K. R., Knowlton, K. U. (2003) The suppressor of cytokine signaling-1 (SOCS1) is a novel therapeutic target for enterovirus-induced cardiac injury. J Clin. Invest. 111: 469-478.
Yen, M. H., Tsao, K. C., Huang, Y. C., Huang, C. G,m Huang, Y. L., Lin, R., Chang, M. L., Huang, C. C., Yan, D. C., Lin, Z. Y. (2007) Viral load in blood is correlated with disease severity of neonatal coxsackievirus B3 infection: early diagnosis and predicting disease severity is possible in severe neonatal enterovirus infection. Clin Infect Dis. 44: e78-81.
Zautner, A. E., Körner, U., Henke, A., Badorff, C., Schmidtke, M. (2003) Heparan sulfates and coxsackievirus-adenovirus receptor: each one mediates coxsackievirus B3 PD infection. J Virol. 77: 10071-10077.
Zinkernagel, R. M. (2001) Maternal antibodies, childhood infections, and autoimmune diseases. N Engl J Med. 345: 1331-1335.
Zimmermann, H., Sidler, S., Gassler, N., Nattermann, J., Luedde, T., Trautwein, C., Tacke, F. (2011) Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One 6: e21381.
劉蓉燕 (中華民國九十五年) 克沙奇B3病毒引起肝炎之體外及體內模式的研究， 國立成功大學微生物暨免疫學研究所碩士論文。