α-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors
α-Defensins can have anti-HIV activity but are not CD8 cell anti-HIV factors
复制标题
DOI：
10.1097/00002030-200309260-00001
复制
发表时间：
2003-09-26
期刊：
影响因子：
3.8
通讯作者：
Levy, JA
中科院分区：
文献类型：
--
作者：
Mackewicz, CE;Yuan, J;Levy, JA
背景：来自健康HIV感染者的CD8 T细胞通过可溶性CD8细胞抗病毒因子（CAF）介导的非细胞毒性机制抑制HIV在感染CD4 T细胞中的复制。最近，有报道称抗微生物肽（α -防御素）构成CAF。目的：研究a-防御素的抗病毒活性，探讨其在CD8细胞非细胞毒性抗病毒反应中的潜在作用。设计和方法：使用纯化的人中性粒细胞蛋白（HNP） 1-3 （α -防御素）混合物来检测α -防御素在感染前或感染后治疗的CD4细胞中对HIV病毒粒子和HIV复制的影响。在CD8细胞以及其他各种细胞类型中分析α -防御素在RNA和蛋白水平上的表达。在CD8细胞培养液中检测防御素抗体抑制CAF活性的能力。结果：α -防御素至少在两个层面上表现出抗hiv活性：直接灭活病毒颗粒；并影响目标CD4细胞复制病毒的能力。然而，虽然我们可以在中性粒细胞和单核细胞中证明α -防御素，但我们没有发现CD8 T细胞产生这些肽的证据。在纯化的CD8 T细胞中没有检测到编码这些蛋白的信使RNA，这些细胞也不产生细胞内或细胞外的a -防御素肽。此外，针对人α -防御素1、2和3的特异性抗体不会阻断caf8细胞培养液的抗病毒活性。结论：α -防御素不是由CD8细胞产生的，但意外地发现在单核细胞中表达。α -防御素具有抗hiv活性，但不是CD8细胞抗病毒因子。(C) 2003利平科特·威廉姆斯·威尔金斯。
Background: CD8 T cells from healthy HIV-infected individuals inhibit HIV replication in infected CD4 T cells by a non-cytotoxic mechanism mediated by a soluble CD8 cell antiviral factor, CAF Recently, the antimicrobial peptides, alpha-defensins, were reported to constitute CAF.Objective: To examine the antiviral activity of a-defensins and address their potential role in CD8 cell non-cytotoxic antiviral responses.Design and methods: A purified mixture of human neutrophil proteins (HNP) 1-3 (alpha-defensins) was used to examine the effect of alpha-defensins on HIV virions and on HIV replication in CD4 cells treated prior to or post infection. alpha-Defensin expression was analyzed at the RNA and protein level in CD8 cells as well as in various other cell types. Antibodies to the defensins were tested for their ability to inhibit CAF activity in CD8 cell culture fluids.Results: The alpha-defensins exhibited anti-HIV activity on at least two levels: directly inactivating virus particles; and affecting the ability of target CD4 cells to replicate the virus. However, while we could demonstrate alpha-defensins in neutrophils and monocytes, we found no evidence for the production of these pepticles by CD8 T cells. No messenger RNA encoding these proteins was detected in purified CD8 T cells, nor did these cells produce intracellular or extracellular a.-defensin peptides. Moreover, antibodies specific for human alpha-defensins 1, 2, and 3 did not block the antiviral activity of CAF-active CD8 cell culture fluids.Conclusions: The alpha-defensins are not produced by CD8 cells but unexpectedly were found to be expressed in monocytes. alpha-Defensins can have anti-HIV activity but are not CD8 cell antiviral factors. (C) 2003 Lippincott Williams Wilkins.