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系統識別號 U0026-2107201117121900
論文名稱(中文) 探討galectin-1對於流行性感冒病毒感染的作用機制 及治療效果
論文名稱(英文) Mechanisms of action and therapeutic efficacy of galectin-1 in influenza virus infection
校院名稱 成功大學
系所名稱(中) 基礎醫學研究所
系所名稱(英) Institute of Basic Medical Sciences
學年度 99
學期 2
出版年 100
研究生(中文) 楊玫琳
研究生(英文) Mei-Lin Yang
學號 s5894108
學位類別 博士
語文別 英文
論文頁數 73頁
口試委員 指導教授-蕭璦莉
口試委員-吳文鑾
口試委員-林以行
召集委員-王憲威
口試委員-何美鄉
口試委員-王金和
中文關鍵字 流行性感冒病毒  lectin  galectin-1  抗病毒  金奈米 
英文關鍵字 influenza virus  lectin  galectin-1  antiviral  gold nanoparticle 
學科別分類
中文摘要 流行性感冒病毒為目前人類及動物的重要感染疾病之一。為了有效控制及防禦流感病毒的感染,發展新型且有效抑制病毒感染的疫苗及藥物是必須的。先天免疫系統對於流感病毒感染及清除病毒上扮演了重要的角色,過去研究指出當呼吸道受到感染時會有一群lectin蛋白家族透過與病毒結合進而抑制病毒活性。Galectin-1為β-galactoside的結合蛋白,屬於S-type lectin蛋白家族的一員,目前已知其會利用C端醣類辨識區辨識並與病毒套膜上的醣類蛋白結合。由於流感病毒套膜蛋白上含有豐富的醣基化現象,因此我們想進一步探討galectin-1在流感病毒感染上所扮演的角色為何以及評估galectin-1做為治療流感病毒感染的效用。首先,從我們的初步實驗結果顯示,在小鼠感染流感後,galectin-1在肺灌洗液及肺組織表現量和病毒量具有正相關的增加。在in vitro的實驗中,MDCK細胞以galectin-1蛋白直接處理後,較能夠抑制病毒複製及感染能力,進而提升細胞存活。在小鼠實驗中,由鼻腔給予galectin-1也可減少肺部病毒含量及細胞死亡,進而減緩體重下降和降低小鼠死亡率。接著探討內生性galectin-1對於病毒感染的作用,galectin-1 knockout小鼠比起wild-type小鼠則較容易受到流感病毒感染而死亡。透過ELISA、電子顯微鏡的分析及表面等離子共振技術,發現galectin-1會直接與流感病毒套膜上醣蛋白結合,因此影響病毒的感染力及血球凝集反應,而這樣的結合現象也發生於其他亞型的流感病毒中,解離常數(Kd)約為0.6至1.3 × 10-6 M。由於galectin-1結合至金奈米(gold nanoparticle)上後,可透過多價鍵的方式增強與病毒的結合,因此我們使用金奈米作為加強galectin-1 (AuNP/Gal-1)抑制病毒功能的載體。我們初步發現,AuNP/Gal-1比起單獨galectin-1對於抑制病毒感染的能力較為穩定且不會對正常細胞造成毒性。接著分析AuNP/Gal-1可提高與多種亞型流感病毒結合的親和力(Kd ~10-9 M),並且降低50%有效抑制病毒感染的濃度(EC50) 50至100倍。另一方面我們將AuNP/Gal-1應用於保護小鼠不受病毒感染的實驗上,給予AuNP/Gal-1治療的小鼠減緩體重下降且肺部有比較少的細胞浸潤及病毒量。最後利用表面等離子共振技術分析,AuNP/Gal-1透過聚集流感病毒造成較大的波長偏移,因此可專一性的辨識不同亞型的流感病毒。綜合以上結果,galectin-1藉由與流感病毒表面蛋白結合進而抑制病毒感染能力,而利用金奈米則可加強galectin-1功能,提供較強的多價鍵結,因而提高與病毒的親和力。因此我們認為galectin-1與AuNP/Gal-1可發展做為新型抑制流感病毒感染的藥物。
英文摘要 Influenza is an important infectious disease in humans and animals. For the prevention and control of influenza, development of improved and novel vaccines and antiviral drugs is required. Innate immune response is important for viral clearance during influenza virus infection. Galectin-1, which belongs to S-type lectins, contains a conserved carbohydrate recognition domain that recognizes galactose-containing oligosaccharides. As the envelope proteins of influenza virus are highly glycosylated, in this study we studied the role of galectin-1 and evaluated its therapeutic efficacy in influenza virus infection. In mice, galectin-1 was upregulated in the lung during influenza virus infection. There was a positive correlation between galectin-1 levels and viral loads during the acute phase of viral infection. Cells treated with recombinant human galectin-1 generated lower viral yields after influenza virus infection. In animal studies, intranasal treatment of galectin-1 could enhance survival of mice against lethal challenge with influenza virus by reducing viral load, inflammation, and apoptosis in the lung. Furthermore, galectin-1 knockout mice were more susceptible to influenza virus infection than wild-type mice. In addition, galectin-1 could directly bind to the envelope glycoproteins of influenza A/WSN/33 virus and inhibit its hemagglutination activity. It also bound to different subtypes of influenza A virus with micromolar dissociation constant (Kd) values. We employed gold nanoparticle (AuNP), surface plasmon resonance (SPR) analysis, and transmission electron microscopy (TEM) to further demonstrate the direct binding of galectin-1 to influenza virus. Because the conjugation of galectin-1 onto AuNP provides a means to enhance the binding of galectin-1 to influenza virus through multivalent interactions, we fabricated galectin-1-functionalized AuNP (AuNP/Gal-1) aiming at enhancing the anti-influenza virus activity of galectin-1. We found that AuNP/Gal-1 nanocomplex was more stable than free galectin-1 in maintaining the anti-influenza virus activity and had no significant cytotoxicity to normal lung cells. Compared to free galectin-1, the binding affinity of AuNP/Gal-1 to several subtypes of influenza virus was dramatically increased with Kd values of ~10-9 M, and the 50% effective concentration (EC50) values of AuNP/Gal-1 for protecting cells from influenza virus-induced cytopathic effect (CPE) were reduced by ~50- to 100-fold. Influenza virus-infected mice treated with AuNP/Gal-1 exhibited less damage and fewer virus-infected cells in the lung. Furthermore, mice infected with influenza virus admixed with AuNP/Gal-1 were protective against viral infection. Finally, specific recognition for influenza virus by AuNP/Gal-1 induced a red shift of the SPR band, which may be exploited for developing a novel detection system for influenza virus. Collectively, our results indicate that galectin-1 has anti-influenza virus activity by binding to viral surface and inhibiting its infectivity. Moreover, galectin-1 conjugated on AuNP can enhance the anti-influenza activity of galectin-1 by providing high local concentrations and multivalent interactions. Thus, both galectin-1 and AuNP/Gal-1 may be further explored as novel broad-spectrum inhibitors of influenza virus infection.
論文目次 Contents
Qualified Certificate I
Acknowlegements II
Chinese Abstract III
English Abstract V
Contents VII
Index of Table VIII
Index of Figures IX
Abbreviations XI
Introduction 1
Materials and Methods 11
Results 22
Discussion 34
Conclusion 41
References 42
Table 49
Figures 50
Appendix 73
參考文獻 References
1. Akaike, T., Y. Noguchi, S. Ijiri, K. Setoguchi, M. Suga, Y. M. Zheng, B. Dietzschold, and H. Maeda. 1996. Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proceedings of the National Academy of Sciences 93:2448-2453.
2. Almkvist, J., C. Dahlgren, H. Leffler, and A. Karlsson. 2002. Activation of the neutrophil nicotinamide adenine dinucleotide phosphate oxidase by galectin-1. J Immunol 168:4034-4041.
3. Avni, O., Z. Pur, E. Yefenof, and M. Baniyash. 1998. Complement receptor 3 of macrophages is associated with galectin-1-like protein. J Immunol 160:6151-6158.
4. Barrionuevo, P., M. Beigier-Bompadre, J. M. Ilarregui, M. A. Toscano, G. A. Bianco, M. A. Isturiz, and G. A. Rabinovich. 2007. A novel function for galectin-1 at the crossroad of innate and adaptive immunity: galectin-1 regulates monocyte/macrophage physiology through a nonapoptotic ERK-dependent pathway. J Immunol 178:436-445.
5. Borron, P. J., E. C. Crouch, J. F. Lewis, J. R. Wright, F. Possmayer, and L. J. Fraher. 1998. Recombinant rat surfactant-associated protein D inhibits human T lymphocyte proliferation and IL-2 production. J Immunol 161:4599-4603.
6. Bowman, M.-C., T. E. Ballard, C. J. Ackerson, D. L. Feldheim, D. M. Margolis, and C. Melander. 2008. Inhibition of HIV Fusion with Multivalent Gold Nanoparticles. Journal of the American Chemical Society 130:6896-6897.
7. Brandt, B., T. Büchse, E. Abou-Eladab, M. Tiedge, E. Krause, U. Jeschke, and H. Walzel. 2008. Galectin-1 induced activation of the apoptotic death-receptor pathway in human Jurkat T lymphocytes. Histochemistry and Cell Biology 129:599-609.
8. Chen, Y.-C., C.-H. Chen, and C.-H. Wang. 2008. H5 antibody detection by blocking enzyme-linked immunosorbent assay using a monoclonal antibody. Avian Diseases 52:124-129.
9. Chu, V. C., and G. R. Whittaker. 2004. Influenza virus entry and infection require host cell N-linked glycoprotein. Proceedings of the National Academy of Sciences of the United States of America 101:18153-18158.
10. Cook, D., M. Beck, T. Coffman, S. Kirby, J. Sheridan, I. Pragnell, and O. Smithies. 1995. Requirement of MIP-1 alpha for an inflammatory response to viral infection. Science 269:1583-1585.
11. Cooper, D., L. V. Norling, and M. Perretti. 2008. Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow. J Leukoc Biol 83:1459-1466.
12. Correa, S. G., C. E. Sotomayor, M. P. Aoki, C. A. Maldonado, and G. A. Rabinovich. 2003. Opposite effects of galectin-1 on alternative metabolic pathways of L-arginine in resident, inflammatory, and activated macrophages. Glycobiology 13:119-128.
13. Dawson, T. C., M. A. Beck, W. A. Kuziel, F. Henderson, and N. Maeda. 2000. Contrasting effects of CCR5 and CCR2 deficiency in the pulmonary inflammatory response to influenza A virus. Am J Pathol 156:1951-1959.
14. Deom, C. M., A. J. Caton, and I. T. Schulze. 1986. Host cell-mediated selection of a mutant influenza A virus that has lost a complex oligosaccharide from the tip of the hemagglutinin. Proceedings of the National Academy of Sciences 83:3771-3775.
15. Deom, C. M., and I. T. Schulze. 1985. Oligosaccharide composition of an influenza virus hemagglutinin with host-determined binding properties. Journal of Biological Chemistry 260:14771-14774.
16. Deshpande, K. L., V. A. Fried, M. Ando, and R. G. Webster. 1987. Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence. Proceedings of the National Academy of Sciences of the United States of America 84:36-40.
17. Fields, S., G. Winter, and G. G. Brownlee. 1981. Structure of the neuraminidase gene in human influenza virus A/PR/8/34. Nature 290:213-217.
18. Fowler, M., R. J. Thomas, J. Atherton, I. S. Roberts, and N. J. High. 2006. Galectin-3 binds to Helicobacter pylori O-antigen: it is upregulated and rapidly secreted by gastric epithelial cells in response to H. pylori adhesion. Cellular Microbiology 8:44-54.
19. Garner, O. B., H. C. Aguilar, J. A. Fulcher, E. L. Levroney, R. Harrison, L. Wright, L. R. Robinson, V. Aspericueta, M. Panico, S. M. Haslam, H. R. Morris, A. Dell, B. Lee, and L. G. Baum. 2010. Endothelial galectin-1 binds to specific glycans on Nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation. PLoS Pathog 6:e1000993.
20. Gauthier, S., I. Pelletier, M. Ouellet, A. Vargas, M. Tremblay, S. Sato, and B. Barbeau. 2008. Induction of galectin-1 expression by HTLV-I Tax and its impact on HTLV-I infectivity. Retrovirology 5:105.
21. Govorkova, E. A., H.-B. Fang, M. Tan, and R. G. Webster. 2004. Neuraminidase inhibitor-rimantadine combinations exert additive and synergistic anti-influenza virus effects in MDCK cells. Antimicrob. Agents Chemother. 48:4855-4863.
22. Grabar, K. C., R. G. Freeman, M. B. Hommer, and M. J. Natan. 2002. Preparation and characterization of Au colloid monolayers. Analytical Chemistry 67:735-743.
23. Haczku, A., Y. Cao, G. Vass, S. Kierstein, P. Nath, E. N. Atochina-Vasserman, S. T. Scanlon, L. Li, D. E. Griswold, K. F. Chung, F. R. Poulain, S. Hawgood, M. F. Beers, and E. C. Crouch. 2006. IL-4 and IL-13 form a negative feedback circuit with surfactant protein-D in the allergic airway response. J. Immunol. 176:3557-3565.
24. Hartshorn, K. L., M. R. White, V. Shepherd, K. Reid, J. C. Jensenius, and E. C. Crouch. 1997. Mechanisms of anti-influenza activity of surfactant proteins A and D: comparison with serum collectins. Am J Physiol 273:L1156-1166.
25. Hartshorn, K. L., M. R. White, T. Tecle, U. Holmskov, and E. C. Crouch. 2006. Innate defense against influenza A virus: activity of human neutrophil defensins and interactions of defensins with surfactant protein D. J. Immunol. 176:6962-6972.
26. Hartshorn, K. L., M. R. White, D. R. Voelker, J. Coburn, K. Zaner, and E. C. Crouch. 2000. Mechanism of binding of surfactant protein D to influenza A viruses: importance of binding to haemagglutinin to antiviral activity. Biochem J 351 Pt 2:449-458.
27. Hawgood, S., C. Brown, J. Edmondson, A. Stumbaugh, L. Allen, J. Goerke, H. Clark, and F. Poulain. 2004. Pulmonary Collectins Modulate Strain-Specific Influenza A Virus Infection and Host Responses. J. Virol. 78:8565-8572.
28. Hidari, K. I. P. J., T. Murata, K. Yoshida, Y. Takahashi, Y.-h. Minamijima, Y. Miwa, S. Adachi, M. Ogata, T. Usui, Y. Suzuki, and T. Suzuki. 2008. Chemoenzymatic synthesis, characterization, and application of glycopolymers carrying lactosamine repeats as entry inhibitors against influenza virus infection. Glycobiology 18:779-788.
29. Hiti, A. L., and D. P. Nayak. 1982. Complete nucleotide sequence of the neuraminidase gene of human influenza virus A/WSN/33. J. Virol. 41:730-734.
30. Hortobagyi, L., S. Kierstein, K. Krytska, X. Zhu, A. M. Das, F. Poulain, and A. Haczku. 2008. Surfactant protein D inhibits TNF-alpha production by macrophages and dendritic cells in mice. J Allergy Clin Immunol.
31. Horvath, A., I. Andersen, K. Junker, B. Lyck Fogh-Schultz, E. Holm Nielsen, S. Gizurarson, O. Andersen, J. Karman, E. Rajnavolgyi, A. Erdei, and S. E. Svehag. 2001. Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies. Antiviral Research 52:43-53.
32. Hsieh, J.-L., C.-L. Wu, C.-H. Lee, and A.-L. Shiau. 2003. Hepatitis B Virus X Protein Sensitizes Hepatocellular Carcinoma Cells to Cytolysis Induced by E1B-deleted Adenovirus through the Disruption of p53 Function. Clinical Cancer Research 9:338-345.
33. Hsieh, S. H., N. W. Ying, M. H. Wu, W. F. Chiang, C. L. Hsu, T. Y. Wong, Y. T. Jin, T. M. Hong, and Y. L. Chen. 2008. Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene 27:3746-3753.
34. Humphreys, I. R., L. Edwards, R. J. Snelgrove, A. J. Rae, A. J. Coyle, and T. Hussell. 2006. A critical role for ICOS co-stimulation in immune containment of pulmonary influenza virus infection. Eur J Immunol 36:2928-2938.
35. Humphreys, I. R., G. Walzl, L. Edwards, A. Rae, S. Hill, and T. Hussell. 2003. A critical role for OX40 in T cell-mediated immunopathology during lung viral infection. J Exp Med 198:1237-1242.
36. Jack, D. L., M. E. Lee, M. W. Turner, N. J. Klein, and R. C. Read. 2005. Mannose-binding lectin enhances phagocytosis and killing of Neisseria meningitidis by human macrophages. J Leukoc Biol 77:328-336.
37. Jia, W., H. Li, and Y. W. He. 2008. Pattern recognition molecule mindin promotes intranasal clearance of influenza viruses. J Immunol 180:6255-6261.
38. Jiang, W., Y. S. KimBetty, J. T. Rutka, and C. W. ChanWarren. 2008. Nanoparticle-mediated cellular response is size-dependent. Nat Nano 3:145-150.
39. Kobasa, D., S. M. Jones, K. Shinya, J. C. Kash, J. Copps, H. Ebihara, Y. Hatta, J. H. Kim, P. Halfmann, M. Hatta, F. Feldmann, J. B. Alimonti, L. Fernando, Y. Li, M. G. Katze, H. Feldmann, and Y. Kawaoka. 2007. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445:319-323.
40. Krishnamoorthy, L., J. W. Bess, A. B. Preston, K. Nagashima, and L. K. Mahal. 2009. HIV-1 and microvesicles from T cells share a common glycome, arguing for a common origin. Nat Chem Biol 5:244-250.
41. Le Goffic, R., V. Balloy, M. Lagranderie, L. Alexopoulou, N. Escriou, R. Flavell, M. Chignard, and M. Si-Tahar. 2006. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog 2:e53.
42. Lee, R. T., and Y. C. Lee. 2000. Affinity enhancement by multivalent lectin–carbohydrate interaction. Glycoconjugate Journal 17:543-551.
43. Lehrer, R. I., G. Jung, P. Ruchala, S. Andre, H. J. Gabius, and W. Lu. 2009. Multivalent Binding of Carbohydrates by the Human {alpha}-Defensin, HD5. J Immunol 183:480-490.
44. Leppanen, A., S. Stowell, O. Blixt, and R. D. Cummings. 2005. Dimeric galectin-1 binds with high affinity to alpha2,3-sialylated and non-sialylated terminal N-acetyllactosamine units on surface-bound extended glycans. J Biol Chem 280:5549-5562.
45. LeVine, A. M., J. A. Whitsett, K. L. Hartshorn, E. C. Crouch, and T. R. Korfhagen. 2001. Surfactant protein D enhances clearance of influenza A virus from the lung in vivo. J. Immunol. 167:5868-5873.
46. Levroney, E. L., H. C. Aguilar, J. A. Fulcher, L. Kohatsu, K. E. Pace, M. Pang, K. B. Gurney, L. G. Baum, and B. Lee. 2005. Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines. The Journal of Immunology 175:413-420.
47. Levroney, E. L., H. C. Aguilar, J. A. Fulcher, L. Kohatsu, K. E. Pace, M. Pang, K. B. Gurney, L. G. Baum, and B. Lee. 2005. Novel innate immune functions for galectin-1: galectin-1 inhibits cell fusion by Nipah virus envelope glycoproteins and augments dendritic cell secretion of proinflammatory cytokines. J Immunol 175:413-420.
48. Li, H., Y. Guan, A. Szczepanska, A. J. Moreno-Vargas, A. T. Carmona, I. Robina, G. K. Lewis, and L.-X. Wang. 2007. Synthesis and anti-HIV activity of trivalent CD4-mimetic miniproteins. Bioorganic & Medicinal Chemistry 15:4220-4228.
49. Lin, K. L., Y. Suzuki, H. Nakano, E. Ramsburg, and M. D. Gunn. 2008. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J. Immunol. 180:2562-2572.
50. Malik Peiris, J. S., L. L. M. Poon, and Y. Guan. 2009. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans. Journal of Clinical Virology 45:169-173.
51. Matrosovich, M., and H.-D. Klenk. 2003. Natural and synthetic sialic acid-containing inhibitors of influenza virus receptor binding. Reviews in Medical Virology 13:85-97.
52. Matsubara, T., M. Sumi, H. Kubota, T. Taki, Y. Okahata, and T. Sato. 2009. Inhibition of Influenza Virus Infections by Sialylgalactose-Binding Peptides Selected from a Phage Library. Journal of Medicinal Chemistry 52:4247-4256.
53. Mercier, S., C. St-Pierre, I. Pelletier, M. Ouellet, M. J. Tremblay, and S. Sato. 2008. Galectin-1 promotes HIV-1 infectivity in macrophages through stabilization of viral adsorption. Virology 371:121-129.
54. Meschi, J., E. C. Crouch, P. Skolnik, K. Yahya, U. Holmskov, R. Leth-Larsen, I. Tornoe, T. Tecle, M. R. White, and K. L. Hartshorn. 2005. Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication. J Gen Virol 86:3097-3107.
55. Mitnaul, L. J., M. N. Matrosovich, M. R. Castrucci, A. B. Tuzikov, N. V. Bovin, D. Kobasa, and Y. Kawaoka. 2000. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J. Virol. 74:6015-6020.
56. Mukherjee, P., R. Bhattacharya, P. Wang, L. Wang, S. Basu, J. A. Nagy, A. Atala, D. Mukhopadhyay, and S. Soker. 2005. Antiangiogenic Properties of Gold Nanoparticles. Clinical Cancer Research 11:3530-3534.
57. Neumann, G., T. Noda, and Y. Kawaoka. 2009. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 459:931-939.
58. Nieminen, J., C. St-Pierre, P. Bhaumik, F. Poirier, and S. Sato. 2008. Role of galectin-3 in leukocyte recruitment in a murine model of lung infection by Streptococcus pneumoniae. The Journal of Immunology 180:2466-2473.
59. Nunoi, H., M. R. Mercado, T. Mizukami, K. Okajima, T. Morishima, H. Sakata, S. Nakayama, S. Mori, M. Hayashi, H. Mori, S. Kagimoto, S. Kanegasaki, K. Watanabe, N. Adachi, and F. Endo. 2005. Apoptosis under hypercytokinemia is a possible pathogenesis in influenza-associated encephalopathy. Pediatrics International 47:175-179.
60. Ogata, M., K. I. P. J. Hidari, W. Kozaki, T. Murata, J. Hiratake, E. Y. Park, T. Suzuki, and T. Usui. 2009. Molecular Design of Spacer-N-Linked Sialoglycopolypeptide as Polymeric Inhibitors Against Influenza Virus Infection. Biomacromolecules 10:1894-1903.
61. Ouellet, M., S. Mercier, I. Pelletier, S. Bounou, J. Roy, J. Hirabayashi, S. Sato, and M. J. Tremblay. 2005. Galectin-1 acts as a soluble host factor that promotes HIV-1 infectivity through stabilization of virus attachment to host cells. The Journal of Immunology 174:4120-4126.
62. Papp, I., C. Sieben, K. Ludwig, M. Roskamp, C. Böttcher, S. Schlecht, A. Herrmann, and R. Haag. 2010. Inhibition of influenza virus infection by multivalent sialic-acid-functionalized gold nanoparticles. Small 6:2900-2906.
63. Perone, M. J., A. T. Larregina, W. J. Shufesky, G. D. Papworth, M. L. Sullivan, A. F. Zahorchak, D. B. Stolz, L. G. Baum, S. C. Watkins, A. W. Thomson, and A. E. Morelli. 2006. Transgenic galectin-1 induces maturation of dendritic cells that elicit contrasting responses in naive and activated T cells. J Immunol 176:7207-7220.
64. Poirier, F., and E. J. Robertson. 1993. Normal development of mice carrying a null mutation in the gene encoding the L14 S-type lectin. Development 119:1229-1236.
65. Rabinovich, G. A., F. T. Liu, M. Hirashima, and A. Anderson. 2007. An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer. Scandinavian Journal of Immunology 66:143-158.
66. Rabinovich, G. A., M. A. Toscano, S. S. Jackson, and G. R. Vasta. 2007. Functions of cell surface galectin-glycoprotein lattices. Current Opinion in Structural Biology 17:513-520.
67. Reading, P., D. Pickett, M. Tate, P. Whitney, E. Job, and A. Brooks. 2009. Loss of a single N-linked glycan from the hemagglutinin of influenza virus is associated with resistance to collectins and increased virulence in mice. Respiratory Research 10:117.
68. Reading, P. C., S. Bozza, B. Gilbertson, M. Tate, S. Moretti, E. R. Job, E. C. Crouch, A. G. Brooks, L. E. Brown, B. Bottazzi, L. Romani, and A. Mantovani. 2008. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J. Immunol. 180:3391-3398.
69. Reading, P. C., L. S. Morey, E. C. Crouch, and E. M. Anders. 1997. Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. J. Virol. 71:8204-8212.
70. Schofield, C. L., R. A. Field, and D. A. Russell. 2007. Glyconanoparticles for the Colorimetric Detection of Cholera Toxin. Analytical Chemistry 79:1356-1361.
71. Schulman, J. L., and P. Palese. 1977. Virulence factors of influenza A viruses: WSN virus neuraminidase required for plaque production in MDBK cells. J. Virol. 24:170-176.
72. Shukla, R., V. Bansal, M. Chaudhary, A. Basu, R. R. Bhonde, and M. Sastry. 2005. Biocompatibility of Gold Nanoparticles and Their Endocytotic Fate Inside the Cellular Compartment: A Microscopic Overview. Langmuir 21:10644-10654.
73. Skehel, J., D. Stevens, R. Daniels, A. Douglas, M. Knossow, I. Wilson, and D. Wiley. 1984. A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc Natl Acad Sci USA 81:1779 - 1783.
74. Skehel, J. J., and D. C. Wiley. 2000. Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annual Review of Biochemistry 69:531-569.
75. Smee, D. F., K. W. Bailey, M.-H. Wong, B. R. O'Keefe, K. R. Gustafson, V. P. Mishin, and L. V. Gubareva. 2008. Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N. Antiviral Research 80:266-271.
76. Sugiura, A., and M. Ueda. 1980. Neurovirulence of influenza virus in mice I. Neurovirulence of recombinants between virulent and avirulent virus strains. Virology 101:440-449.
77. Tam, J. S. 2002. Influenza A (H5N1) in Hong Kong: an overview. Vaccine 20:S77-S81.
78. Thanh, N. T. K., and Z. Rosenzweig. 2002. Development of an aggregation-based immunoassay for anti-protein A using gold nanoparticles. Analytical Chemistry 74:1624-1628.
79. Thielens, N. M., P. Tacnet-Delorme, and G. J. Arlaud. 2002. Interaction of C1q and mannan-binding lectin with viruses. Immunobiology 205:563-574.
80. Toscano, M. A., G. A. Bianco, J. M. Ilarregui, D. O. Croci, J. Correale, J. D. Hernandez, N. W. Zwirner, F. Poirier, E. M. Riley, L. G. Baum, and G. A. Rabinovich. 2007. Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nat Immunol 8:825-834.
81. Totani, K., T. Kubota, T. Kuroda, T. Murata, K. I.-P. J. Hidari, T. Suzuki, Y. Suzuki, K. Kobayashi, H. Ashida, K. Yamamoto, and T. Usui. 2003. Chemoenzymatic synthesis and application of glycopolymers containing multivalent sialyloligosaccharides with a poly(L-glutamic acid) backbone for inhibition of infection by influenza viruses. Glycobiology 13:315-326.
82. Tsai, C.-Y., A.-L. Shiau, S.-Y. Chen, Y.-H. Chen, P.-C. Cheng, M.-Y. Chang, D.-H. Chen, C.-H. Chou, C.-R. Wang, and C.-L. Wu. 2007. Amelioration of collagen-induced arthritis in rats by nanogold. Arthritis & Rheumatism 56:544-554.
83. Vasta, G. R. 2009. Roles of galectins in infection. Nat Rev Micro 7:424-438.
84. Vigerust, D. J., K. B. Ulett, K. L. Boyd, J. Madsen, S. Hawgood, and J. A. McCullers. 2007. N-linked glycosylation attenuates H3N2 influenza viruses. J. Virol. 81:8593 - 8600.
85. Vray, B., I. Camby, V. Vercruysse, T. Mijatovic, N. V. Bovin, P. Ricciardi-Castagnoli, H. Kaltner, I. Salmon, H.-J. Gabius, and R. Kiss. 2004. Up-regulation of galectin-3 and its ligands by Trypanosoma cruzi infection with modulation of adhesion and migration of murine dendritic cells. Glycobiology 14:647-657.
86. Wang, C.-C., J.-R. Chen, Y.-C. Tseng, C.-H. Hsu, Y.-F. Hung, S.-W. Chen, C.-M. Chen, K.-H. Khoo, T.-J. Cheng, Y.-S. E. Cheng, J.-T. Jan, C.-Y. Wu, C. Ma, and C.-H. Wong. 2009. Glycans on influenza hemagglutinin affect receptor binding and immune response. Proceedings of the National Academy of Sciences 106:18137-18142.
87. Wang, C.-W., and C.-H. Wang. 2003. Experimental selection of virus derivatives with variations in virulence from a single low-pathogenicity H6N1 avian influenza virus field isolate. Avian Diseases 47:1416-1422.
88. Wang, C. R., A. L. Shiau, S. Y. Chen, Z. S. Cheng, Y. T. Li, C. H. Lee, Y. T. Yo, C. W. Lo, Y. S. Lin, H. Y. Juan, Y. L. Chen, and C. L. Wu. 2010. Intra-articular lentivirus-mediated delivery of galectin-3 shRNA and galectin-1 gene ameliorates collagen-induced arthritis. Gene Ther 17:1225-1233.
89. Wanzeck, K., K. L. Boyd, and J. A. McCullers. 2011. Glycan Shielding of the Influenza Virus Hemagglutinin Contributes to Immunopathology in Mice. Am. J. Respir. Crit. Care Med. 183:767-773.
90. Welliver, T. P., R. P. Garofalo, Y. Hosakote, K. H. Hintz, L. Avendano, K. Sanchez, L. Velozo, H. Jafri, S. Chavez-Bueno, P. L. Ogra, L. McKinney, J. L. Reed, and R. C. Welliver. 2007. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J. Infect. Dis. 195:1126-1136.
91. White, M., P. Kingma, T. Tecle, N. Kacak, B. Linders, J. Heuser, E. Crouch, and K. Hartshorn. 2008. Multimerization of surfactant protein D, but not its collagen domain, is required for antiviral and opsonic activities related to influenza virus. J. Immunol. 181:7936-7943.
92. Wilson, I. A., J. J. Skehel, and D. C. Wiley. 1981. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 [angst] resolution. Nature 289:366-373.
93. Yingsakmongkon, S., D. Miyamoto, N. Sriwilaijaroen, K. Fujita, K. Matsumoto, W. Jampangern, H. Hiramatsu, C. T. Guo, T. Sawada, T. Takahashi, K. Hidari, T. Suzuki, M. Ito, Y. Ito, and Y. Suzuki. 2008. In vitro inhibition of human influenza A virus infection by fruit-juice concentrate of Japanese plum (Prunus mume SIEB. et ZUCC). Biol Pharm Bull 31:511-515.
94. Yu, P., N. Sabine, L. Annika, F. Monika, W. Fei, S. Ulrich, S. Gter, B. Wolfgang, and J.-D. Willi. 2007. Size-Dependent Cytotoxicity of Gold Nanoparticles. Small 3:1941-1949.
95. Zhou, J., M. Matsuoka, H. Cantor, R. Homer, and R. I. Enelow. 2008. Cutting edge: engagement of NKG2A on CD8+ effector T cells limits immunopathology in influenza pneumonia. J Immunol 180:25-29.
96. Zhou, Q., and R. D. Cummings. 1993. L-14 Lectin Recognition of Laminin and Its Promotion of in Vitro Cell Adhesion. Arch. Biochem. Biophy. 300:6-17.

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