Interactions of α-, β-, and θ-Defensins with Influenza A Virus and Surfactant Protein D
Interactions of α-, β-, and θ-Defensins with Influenza A Virus and Surfactant Protein D
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DOI：
10.4049/jimmunol.0804049
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发表时间：
2009-06-15
影响因子：
4.4
通讯作者：
Hartshorn, Kevan L.
中科院分区：
文献类型：
--
作者：
Doss, Mona;White, Mitchell R.;Hartshorn, Kevan L.
我们已经报道了α -防御素人中性粒细胞肽(HNP)-1和HNP-2中和和聚集甲型流感病毒（IAV），并促进中性粒细胞对IAV的摄取。这些α -防御素也被证明与表面活性剂蛋白(SP)-D结合并降低其抗病毒活性。在这项研究中，我们检测了在某些非人灵长类动物的白细胞中发现的抗病毒-防御素的人源化版本逆转录细胞素（RC）1和RC2。RC1在中和IAV方面与HNP-1-3一样有效，RC2和RC101 （RC1的类似物）更有效。相比之下，人β -防御素（HBDs）表现出较少的中和活性。人防御素5和6（主要由肠道Paneth细胞产生）具有与HNP-1-3相似的病毒中和活性。与HNP-1-3一样，RCs诱导病毒聚集并促进中性粒细胞对IAV的摄取。我们使用表面等离子体共振来评估防御素与SP-D的结合。HBDs、HD6和HNP-4与SP-D的结合最小。HNP-1-3和RCs高亲和力结合SP-D；然而，与HNP-1和HNP-2不同，RCs不抑制SP-D的抗病毒活性。HBDs也没有抑制SP-D的抗病毒活性。鉴于其强大的中和活性和与SP-D的相容性，RCs可能为设计预防或治疗IAV引起的呼吸道感染的治疗方法提供有吸引力的原型。中华免疫学杂志，2009,32(2):778 - 787。
We have reported that the alpha-defensins human neutrophil peptides (HNP)-1 and HNP-2 neutralize and aggregate influenza A virus (IAV) and promote uptake of IAV by neutrophils. These alpha-defensins were also shown to bind to surfactant protein (SP)-D and reduce its antiviral activity. In this study, we examined retrocyclin (RC)1 and RC2, humanized versions of the antiviral theta-defensins found in the leukocytes of certain nonhuman primates. RC1 was just as effective as HNP-1-3 in neutralizing IAV, and RC2 and RC101 (an analog of RC1) were more effective. In contrast, human beta-defensins (HBDs) showed less neutralizing activity. Human defensins 5 and 6 (mainly produced by intestinal Paneth cells) had viral neutralizing activity similar to HNP-1-3. Like HNP-1-3, RCs induced viral aggregation and promoted the uptake of IAV by neutrophils. We used surface plasmon resonance to evaluate binding of defensins to SP-D. HBDs, HD6, and HNP-4 bound minimally to SP-D. HNP-1-3 and RCs bound SP-D with high affinity; however, unlike HNP-1 and HNP-2, RCs did not inhibit SP-D antiviral activity. HBDs also did not inhibit antiviral activity of SP-D. Given their strong neutralizing activity and compatibility with SP-D, RCs may provide attractive prototypes for designing therapeutics that can prevent or treat respiratory infections caused by IAV. The Journal of Immunology, 2009, 182: 7878-7887.