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评估重组猪 SP-D 对各种甲型流感病毒的体外抗病毒特性。

Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro.

机构信息

Erasmus Medical Centre, Rotterdam, The Netherlands.

出版信息

PLoS One. 2011;6(9):e25005. doi: 10.1371/journal.pone.0025005. Epub 2011 Sep 14.

Abstract

The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted.

摘要

流感病毒对抗病毒药物现有类别的耐药性的出现引起了关注,因此需要新型的抗病毒药物,这些药物可以用于治疗或预防。表面活性蛋白 D (SP-D) 属于 C 型凝集素家族,是先天免疫系统的重要效应分子,对细菌和病毒具有活性,包括流感病毒。在本研究中,我们评估了重组猪 SP-D 作为抗流感 A 病毒 (IAV) 的体外抗病毒药物的潜力。为了确定抗病毒活性范围,选择了来自鸟类、猪和人类的 30 种 H1N1、H3N2 和 H5N1 亚型的 IAV 进行敏感性测试。通过血凝抑制试验表明,重组猪 SP-D 比重组人 SP-D 更有效,尤其是更高阶的 SP-D 寡聚体形式具有最强的抗病毒活性。猪 SP-D 对广泛的 IAV 株具有活性,并中和了多种 H1N1 和 H3N2 IAV,包括 2009 年大流行的 H1N1 病毒。使用雪貂和人气管的组织切片,我们证明了重组猪 SP-D 可防止人季节性 H1N1 和 H3N2 病毒与上呼吸道上皮细胞上的受体结合。因此,重组猪 SP-D 有望成为一种新型的抗流感病毒药物,进一步的体内开发和评估似乎是合理的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dd3/3173486/1cec0a41dc42/pone.0025005.g001.jpg

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