Functional diversity of anti-lipopolysaccharide factor isoforms in shrimp and their characters related to antiviral activity.

Functional diversity of anti-lipopolysaccharide factor isoforms in shrimp and their characters related to antiviral activity.
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虾抗脂多糖因子异构体的功能多样性及其与抗病毒活性相关的特征

DOI:
10.3390/md13052602
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发表时间:
2015-04-27
期刊:
影响因子:
5.4
通讯作者:
Xiang J
Xiang J
中科院分区:
医学2区
文献类型:
--
作者:
Li S;Guo S;Li F;Xiang J

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抗脂多糖因子(ALF)是一种具有广谱抗菌活性的小分子蛋白质,在疾病防治中具有潜在的应用价值。在此之前,我们从中国明对虾中分离出了7种ALF亚型。本研究对它们在对虾组织中的分布进行了分析,结果表明不同的异构体具有不同的表达谱,提示它们可能具有不同的功能。然后,通过化学合成的ALFs功能域--脂多糖结合域(LBD)的抗菌和抗病毒活性,研究了不同异构体的功能。不同的ALFs表现出不同的抗菌和抗病毒活性,这与其不同的组织分布模式是一致的。对不同亚型的LBD结构域的序列分析表明,具有抗WSSV活性的肽段中具有相同的赖氨酸残基位点。为了确认该赖氨酸残基是否对肽的抗病毒活性至关重要,通过改变该位点的残基来合成新的肽。将特异位点的赖氨酸残基改变为其它氨基酸残基,则该肽的抗病毒活性明显降低。当在LBD肽中的该位点用赖氨酸残基取代其他残基而不具有抗WSSV活性时,该肽将获得对WSSV的抗病毒活性。这些结果不仅使我们对F.同时也为开发ALFs作为WSSV潜在的治疗药物提供了线索。
Anti-lipopolysaccharide factor (ALF) is a small protein with broad-spectrum antimicrobial activity, which has potential application in the disease control. Previously, we isolated seven ALF isoforms from the Chinese shrimp Fenneropenaeus chinensis. In the present study, their distributions in tissues of shrimp were analyzed and the data showed that different isoforms had different expression profiles, which suggested that they might have different functions. Then, the functions of different isoforms were studied by analyzing the antibacterial and antiviral activities of the functional domain of ALFs, the LPS-binding domain (LBD), which were synthesized by chemical methods. Different ALFs showed distinct antibacterial and antiviral activities, which were consistent with their diverse tissue distribution patterns. Sequence analysis on the LBD domain of different isoforms revealed that an identical lysine residue site was specifically conserved in peptides with anti-WSSV activity. In order to confirm whether this lysine residue is critical to the antiviral activity of the peptide, new peptides were synthesized by changing residues at this site. Changing the lysine residue at the specific site to other amino acid residue, the antiviral activity of the peptide apparently decreased. While replacing other residue with a lysine residue at this site in LBD peptide without anti-WSSV activity, the peptide will obtain the antiviral activity to WSSV. These results not only showed us a comprehensive understanding on the function of ALFs from F. chinensis, but also provided clues for the development of ALFs as potential therapeutic drugs to WSSV.
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