A型流行性感冒病毒（Influenza A virus, IAV）可引起人類呼吸道疾病的地區性或全球性大流行。半乳糖凝集素(galectin)，屬於S-型凝集素，為動物凝集素(lectin)的成員之一，具有保守的醣類辨識區能夠辨別半乳糖寡糖(galactose-containing oligosaccharides)，並調控多種生物活性。其中半乳糖凝集素1(galectin-1)和半乳糖凝集素3 (galectin-3)是兩個最為廣泛表達的半乳糖凝素成員。在我們實驗室先前的研究指出，galectin-1可藉由與流感病毒的外套膜醣蛋白結合，來抑制其感染性。最近的研究顯示galectin-3在免疫系統的多種細胞類型皆有表現，並參與在對抗微生物感染的過程中。然而，目前對於galectin-3與抗病毒的作用機制尚未研究透徹。因此在本篇研究我們探討流感病毒感染過程中，galectin-3在細胞和生物體內的調控角色為何。首先，我們發現在小鼠肺部組織中，galectin-3的表現量隨著流感病毒複製量而上升，顯示二者之間有正相關的關係。而組織切片結果顯示，感染過程主要由肺部浸潤的巨噬細胞表現galectin-3。一旦將小鼠肺上皮細胞(MLE 12 細胞)的內生性galectin-3降低表現，則細胞受到病毒感染所誘導的細胞病變感受性提高。我們也建構了galectin-3的原核表現載體，並利用大腸桿菌的原核系統生產galectin-3的重組蛋白。而利用慢病毒攜帶galectin-3表現載體提前於小鼠肺部中大量表現時，則在接受流感病毒感染後，galectin-3小鼠組別相較於控制組具有較好的存活率與較少的病毒複製量、細胞激素產生和浸潤細胞數量。然而，在小鼠受到流感病毒感染後再給予galectin-3重組蛋白則不具有治療效果。總結上述結果，本篇研究不僅提供了解galectin-3參與在先天免疫防禦的契機，對於未來治療流感病毒感染也提供新的策略。

Influenza A virus (IAV) can cause epidemics or pandemics of respiratory diseases in humans. Galectins, which belong to S-type lectins, are a family of animal lectins containing conserved carbohydrate recognition domains (CRDs) capable of recognizing galactose-containing oligosaccharides with diverse biological activities. Galectin-1 and galectin-3 are two most ubiquitously expressed galectins. We have reported previously that galectin-1 can bind to the envelope glycoproteins of influenza virus and inhibit its infectivity. Recent studies have revealed that galectin-3 is expressed in a variety of immune cell types during microbial invasion. However, the effects of galectin-3 in antiviral responses have not been elucidated. In this study, we investigated the role of galectin-3 in IAV infection in vitro and in mouse models. We found that galectin-3 expression increased in the lungs of mice during IAV infection and that its expression level was positively correlated with viral loads in the lung. Histopathological analysis demonstrated that macrophages expressed galectin-3 in the lungs during IAV infection. Knockdown of endogenous galectin-3 rendered murine lung epithelial cells (MLE-12) more susceptible to IAV-induced cytopathic effects. We also constructed a prokaryotic galecitn-3 expression vector and produced recombinant galectin-3 protein in E. coli. Prophylactic treatment of lentiviral vectors encoding galectin-3 enhanced the survival and decreased the viral load, cytokine production, and immune cell infiltration in IAV-infected mice. However, post-treatment of the recombinant galectin-3 protein o exert therapeutic effect in IAV-infected mice. Collectively, this study not only provides opportunities for an understanding of galectin-3 in innate host defense, but also sheds insights into novel therapeutic strategies for combating influenza.

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Bhaumik, P., St-Pierre, G., Milot, V., St-Pierre, C., and Sato, S. (2013). Galectin-3 facilitates neutrophil recruitment as an innate immune response to a parasitic protozoa cutaneous infection. Journal of Immunology 190, 630-640.
Boscher, C., Dennis, J.W., and Nabi, I.R. (2011). Glycosylation, galectins and cellular signaling. Current Opinion in Cell Biology 23, 383-392.
Claas, E.C., Osterhaus, A.D., van Beek, R., De Jong, J.C., Rimmelzwaan, G.F., Senne, D.A., Krauss, S., Shortridge, K.F., and Webster, R.G. (1998). Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 351, 472-477.
Cook, D.N. (1996). The role of MIP-1 alpha in inflammation and hematopoiesis. Journal of Leukocyte Biology 59, 61-66.
de Boer, R.A., Yu, L., and van Veldhuisen, D.J. (2010). Galectin-3 in cardiac remodeling and heart failure. Current Heart Failure Reports 7, 1-8.
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Drickamer, K. (1988). Two distinct classes of carbohydrate-recognition domains in animal lectins. Journal of Biological Chemistry 263, 9557-9560.
Dumic, J., Dabelic, S., and Flogel, M. (2006). Galectin-3: an open-ended story. Biochimica et Biophysica Acta 1760, 616-635.
Feuk-Lagerstedt, E., Jordan, E.T., Leffler, H., Dahlgren, C., and Karlsson, A. (1999). Identification of CD66a and CD66b as the major galectin-3 receptor candidates in human neutrophils. Journal of Immunology 163, 5592-5598.
Frigeri, L.G., Zuberi, R.I., and Liu, F.T. (1993). Epsilon BP, a beta-galactoside-binding animal lectin, recognizes IgE receptor (Fc epsilon RI) and activates mast cells. Biochemistry 32, 7644-7649.
Fujita, T., Matsushita, M., and Endo, Y. (2004). The lectin-complement pathway--its role in innate immunity and evolution. Immunological Reviews 198, 185-202.
Ge, X.N., Bahaie, N.S., Kang, B.N., Hosseinkhani, M.R., Ha, S.G., Frenzel, E.M., Liu, F.T., Rao, S.P., and Sriramarao, P. (2010). Allergen-induced airway remodeling is impaired in galectin-3-deficient mice. Journal of Immunology 185, 1205-1214.
Haudek, K.C., Patterson, R.J., and Wang, J.L. (2010). SR proteins and galectins: what's in a name? Glycobiology 20, 1199-1207.
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