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在转基因小鼠乳汁中表达的重组猪乳铁蛋白可保护新生小鼠免受71型肠道病毒的致命攻击。

Recombinant porcine lactoferrin expressed in the milk of transgenic mice protects neonatal mice from a lethal challenge with enterovirus type 71.

作者信息

Chen Hsiao-Ling, Wang Li-Chung, Chang Chi-Hsuan, Yen Chih-Ching, Cheng Winston T K, Wu Shinn-Chih, Hung Che-Ming, Kuo Meng-Fu, Chen Chuan-Mu

机构信息

Department of Molecular Biotechnology, Da-Yeh University, Changhwa 51501, Taiwan.

出版信息

Vaccine. 2008 Feb 13;26(7):891-8. doi: 10.1016/j.vaccine.2007.12.013. Epub 2008 Jan 3.

Abstract

The human Enterovirus genus of the piconavirus family causes most of the febrile illnesses that affect children during the summer season in Taiwan. Enterovirus type 71 (EV71) plays a key role in patients with hand-foot-and-mouth disease (HFMD) combined with severe paralysis or encephalitis. It is important to find a method for preventing infection with EV71 since there is no antiviral agent or vaccine for humans. In this study, we developed a transgenic mouse model for demonstrating the protective effects of recombinant lactoferrin (LF) against EV71 infection. Transgenic mice carrying alpha-lactalbumin-porcine lactoferrin (alphaLA-pLF) and BALB/c wild-type mice were subjected to EV71 inoculation. First, we analyzed the expression efficiencies of recombinant pLF (rpLF) in hemizygous and homozygous transgenic mice. Following EV71 inoculation on the 4th day of life, pups ingesting transgenic milk showed the significantly higher survival rate and heavier body weight compared to wild-type mice. RT-PCR analysis for EV71 viral RNA showed that the recombinant pLF had a blocking effect on EV71 infection. Our data suggest that oral intake of pLF-enriched milk exhibited the ability to prevent infection with EV71. The study also provides an animal model for validating the protective effects of pLF.

摘要

微小核糖核酸病毒科的人类肠道病毒属引发了台湾夏季影响儿童的大多数发热性疾病。71型肠道病毒(EV71)在患有手足口病(HFMD)并伴有严重瘫痪或脑炎的患者中起关键作用。由于尚无针对人类的抗病毒药物或疫苗,因此找到预防EV71感染的方法很重要。在本研究中,我们建立了一种转基因小鼠模型,以证明重组乳铁蛋白(LF)对EV71感染的保护作用。对携带α-乳白蛋白-猪乳铁蛋白(αLA-pLF)的转基因小鼠和BALB/c野生型小鼠进行EV71接种。首先,我们分析了重组pLF(rpLF)在半合子和纯合子转基因小鼠中的表达效率。在出生后第4天接种EV71后,与野生型小鼠相比,摄入转基因牛奶的幼崽存活率显著更高,体重也更重。对EV71病毒RNA的RT-PCR分析表明,重组pLF对EV71感染具有阻断作用。我们的数据表明,口服富含pLF的牛奶具有预防EV71感染的能力。该研究还提供了一个用于验证pLF保护作用的动物模型。

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