乳鐵蛋白(Lactoferrin; LF)為一種和鐵離子結合的醣蛋白，乳鐵蛋白廣泛的分佈於哺乳動物的體液中，例如：母乳、唾液及分泌的黏液。我們知道在血漿中乳鐵蛋白具有運送金屬離子的能力，但自從1979年之後，科學家陸續發現乳鐵蛋白在非特異性的免疫反應中也扮演了重要的角色，並可抑制某一些微生物的感染(包括有微生物、黴菌、及一些病毒)。因此在本研究中，我們擬進一步的了解乳鐵蛋白對於抑制腸病毒71型及登革病毒血清型第二型感染的影響。腸病毒71型及登革病毒的感染是威脅台灣居民的兩個重大的傳染病，腸病毒71型感染主要造成手口足病，亦會引起中樞神經症狀併發肺水腫而導致死亡。而登革病毒感染一般會自動痊癒，但少數人會發展成致命的登革出血熱及登革休克症候群。我們發現不同濃度的乳鐵蛋白可以抑制腸病毒71型及登革病毒在體外感染細胞，其 IC50分別為34.5 g/ml及67.6 g/ml 。乳鐵蛋白不只可以抑制腸病毒71型及登革病毒的感染，而且在病毒感染後加入大於IC90的乳鐵蛋白依然可以降低病毒的效價。我們在酵素免疫分析法(將細胞固定在96孔盤中)、免疫螢光染色及免疫沉澱法的結果中發現乳鐵蛋白可以直接和細胞膜表面的不同分子結合。我們同樣的在酵素免疫分析法(將病毒及腸病毒71型表面抗原VP1固定在96孔盤中)與競爭法的結果中發現乳鐵蛋白也可以直接和病毒結合。我們更進一步的利用Far-western blot 的方式發現乳鐵蛋白或許是跟腸病毒71型的表面抗原VP1及登革病毒的表面抗原E protein結合。除此之外，我們也發現乳鐵蛋白可以刺激免疫細胞產生IFN-，並且會抑制腸病毒刺激細胞產生的IL-6及MIF。在動物體內，乳鐵蛋白也可以保護受腸病毒71型感染的ICR小鼠並且減緩其病程。綜合上述結果，乳鐵蛋白在抗病毒及免疫刺激的效果中均有很好的成效，未來或許可以將乳鐵蛋白運用在治療或預防腸病毒71型及登革病毒感染所引起的疾病。

　　Lactoferrin (LF) is an iron binding glycoprotein present in some biological fluids of mammals, such as milk, saliva, and mucous secretions. The well-studied function of LF is responsible for the transportation of metals in plasma. However, recent studies have revealed that LF plays an important role in non-specific immune system against many bacterial infection as well as viral agents. In this study we have investigated the antiviral activities of LF against enterovirus71 (EV71) which causes hand, food and mouth disease, pulmonary edema and encephalomyelitis as well as dengue virus (DV), which is the most important arthropod-borne human pathogen, and results in severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). We found that the infection of EV71 and DV can be inhibited by different doses of bovine LF (IC50 is 34.5 g/ml and 67.6 g/ml, respectively). LF not only could prevent EV71 and DV infection, but could also decrease virus titer when target cells were treated with LF at IC90 dose at post-infection stage. Using target cell coated-96 wells plate、IFA and immunoprecipitatioin, we found LF could bind directly to target cells. We also used virus and VP1 of EV71 coated-96 wells plate and competition assay, and found LF could also bind directly to virus. Furthermore, using Far-Western blot, we found that LF can bind to VP1 caspid protein of EV71 and the E protein of DV, both proteins are account for the binding of the viruses to the cells. In addition to no-cytotoxicity to the target cell, LF can induce IFN- expression of host cell. Not only in vitro, LF can also prevent mice from EV71 infection. Therefore, the antiviral as well as immunostimulatory effects of LF make it a promising candidate for the treatment of diseases induced by EV71 and DV.

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