Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37.
Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37.
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DOI：
10.1371/journal.pone.0025333
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Donis RO
中科院分区：
文献类型：
--
作者：
Barlow PG;Svoboda P;Mackellar A;Nash AA;York IA;Pohl J;Davidson DJ;Donis RO
甲型流感病毒在世界范围内引起的广泛发病率和死亡率突出表明需要对宿主免疫反应和新的治疗方法有新的认识。阳离子宿主防御肽（CHDP，也被称为抗菌肽），包括抗菌肽和防御肽，是先天免疫系统的关键成分，在感染和炎症期间上调。抗菌肽具有免疫调节和抗病毒作用，但其对流感病毒感染的影响此前尚未得到评估。因此，我们评估了抗菌肽对甲型流感病毒引起的小鼠疾病的影响。人用抗菌肽LL-37和小鼠用抗菌肽mCRAMP在体内表现出显著的抗病毒活性，在感染小鼠体内降低疾病严重程度和病毒复制，其程度与特性良好的流感病毒特异性抗病毒药物扎那米韦相似。体外和体内实验表明，肽可能直接作用于流感病毒粒子，而不是通过基于受体的机制。用LL-37治疗的流感病毒感染小鼠的肺部促炎细胞因子浓度低于未用抗菌肽治疗的感染小鼠。这些数据表明，用抗菌肽衍生疗法治疗流感感染个体，或调节内源性抗菌肽的产生，可能提供重要的疾病保护。
The extensive world-wide morbidity and mortality caused by influenza A viruses highlights the need for new insights into the host immune response and novel treatment approaches. Cationic Host Defense Peptides (CHDP, also known as antimicrobial peptides), which include cathelicidins and defensins, are key components of the innate immune system that are upregulated during infection and inflammation. Cathelicidins have immunomodulatory and anti-viral effects, but their impact on influenza virus infection has not been previously assessed. We therefore evaluated the effect of cathelicidin peptides on disease caused by influenza A virus in mice. The human cathelicidin, LL-37, and the murine cathelicidin, mCRAMP, demonstrated significant anti-viral activity in vivo, reducing disease severity and viral replication in infected mice to a similar extent as the well-characterized influenza virus-specific antiviral drug zanamivir. In vitro and in vivo experiments suggested that the peptides may act directly on the influenza virion rather than via receptor-based mechanisms. Influenza virus-infected mice treated with LL-37 had lower concentrations of pro-inflammatory cytokines in the lung than did infected animals that had not been treated with cathelicidin peptides. These data suggest that treatment of influenza-infected individuals with cathelicidin-derived therapeutics, or modulation of endogenous cathelicidin production may provide significant protection against disease.
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影响因子：
64.8
作者：
Kash, John C.;Tumpey, Terrence M.;Katze, Michael G.
通讯作者：
Katze, Michael G.
影响因子：
56.9
作者：
Liu, PT;Stenger, S;Modlin, RL
通讯作者：
Modlin, RL
DOI：
10.1016/j.jcf.2003.12.008
发表时间：
2004-03-01
期刊：
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子：
--
作者：
Chen, Christiane I-U;Schaller-Bals, Susanne;Bals, Robert
通讯作者：
Bals, Robert
影响因子：
82.9
作者：
Chromek, Milan;Slamova, Zuzana;Brauner, Annelie
通讯作者：
Brauner, Annelie
影响因子：
4.9
作者：
Fortney, K;Totten, PA;Spinola, SM
通讯作者：
Spinola, SM