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重组乳球菌表达人 LL-37 可预防仔猪和鸡的病毒感染死亡。

Recombinant Lactococcus lactis Expressing Human LL-37 Prevents Deaths from Viral Infections in Piglets and Chicken.

机构信息

Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

Jilin Yuanheyuan Bioengineering Co., Ltd. Changchun, Jilin Province, 130000, China.

出版信息

Probiotics Antimicrob Proteins. 2024 Dec;16(6):2150-2160. doi: 10.1007/s12602-023-10155-6. Epub 2023 Sep 25.

Abstract

Novel antibiotic substitutes are increasingly in demand in the animal husbandry industry. An oral recombinant Lactococcus lactis (L. lactis) expressing human LL-37 (oral LL-37) was developed and its safety and antiviral effectiveness in vivo was tested. In addition to impairing liposome integrity, LL-37 polypeptide from recombinant L. lactis could prevent the host cell infection by a variety of viruses, including recombinant SARS, SARS-CoV-2, Ebola virus, and vesicular stomatitis virus G. Subchronic toxicity studies performed on Sprague-Dawley rats showed that no cumulative toxicity was found during short-term intervention. Oral LL-37 treatment after the onset of fever could reduce mortality in piglets infected with porcine reproductive and respiratory syndrome virus. Moreover, body weight gain of piglets receiving treatment was progressively restored, and nucleic acid positive rebound was not undetected after discontinuation. Oral LL-37 consistently increased the lifespan of chickens infected with Newcastle viruses. These findings suggested a potential use of recombinantly modified microorganisms in veterinary medicine.

摘要

新型抗生素替代品在畜牧业中需求量越来越大。本研究开发了一种表达人 LL-37 的口服重组乳球菌(L. lactis)(口服 LL-37),并对其体内安全性和抗病毒效果进行了测试。除了破坏脂质体完整性外,重组乳球菌中的 LL-37 多肽还可以防止多种病毒(包括重组 SARS、SARS-CoV-2、埃博拉病毒和水疱性口炎病毒 G)感染宿主细胞。对 Sprague-Dawley 大鼠进行的亚慢性毒性研究表明,在短期干预期间未发现累积毒性。在发热后开始口服 LL-37 治疗可降低感染猪繁殖与呼吸综合征病毒的仔猪的死亡率。此外,接受治疗的仔猪的体重逐渐恢复,停药后未检测到核酸阳性反弹。口服 LL-37 可使感染新城疫病毒的鸡的存活时间延长。这些发现提示重组修饰微生物在兽医领域的潜在应用。

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