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PLOS Biol.:树突状细胞有望成为新的治疗艾滋病的靶点

来源:生物谷 2012-12-19 16:49

2012年12月19日讯 /生物谷BIOON/ 现在不能治疗艾滋病的一个重要原因是不知道HIV病毒如何侵入到免疫细胞中。HIV 的主要入侵细胞是T细胞,现在有20多种药物能够阻断HIV在T细胞中的繁殖。HIV通过树突状细胞进入T细胞。现今没有任何药物针对树突状细胞。

前人工作表明HIV表面的一类神经节甘旨(ganglioside),负责识别树突状细胞,在HIV递呈中起重要作用。最新的研究找到了ganglioside在树突状细胞上的对应的结合分子Siglec-1。通过这两种分子的结合,HIV被树突状细胞摄取,最终递呈给T细胞。

研究人员将表达不同量Siglec-1的树突状细胞与HIV混合,发现高剂量的Siglec-1能让更多个HIV进入树突状细胞。并且,抑制Siglec-1活性能够减少HIV进入树突状细胞。这就说明了Siglec-1在HIV入侵树突状细胞中起重要作用,有望成为新的治疗靶点。

研究人员还发现Siglec-1不止帮助HIV进入是树突状细胞,同时还能帮助其他类型病毒进入。这也为我们理解其他类型病毒扩散提供实验依据。(生物谷Bioon.com)

Siglec-1 Is a Novel Dendritic Cell Receptor That Mediates HIV-1 Trans-Infection Through Recognition of Viral Membrane Gangliosides

Nuria Izquierdo-Useros, Maier Lorizate, Maria C. Puertas, Maria T. Rodriguez-Plata, Nadine Zangger, Elina Erikson, Maria Pino, Itziar Erkizia, B?rbel Glass, Bonaventura Clotet, Oliver T. Keppler, Amalio Telenti, Hans-Georg Kr?usslich, Javier Martinez-Picado

Dendritic cells (DCs) are essential antigen-presenting cells for the induction of immunity against pathogens. However, HIV-1 spread is strongly enhanced in clusters of DCs and CD4+ T cells. Uninfected DCs capture HIV-1 and mediate viral transfer to bystander CD4+ T cells through a process termed trans-infection. Initial studies identified the C-type lectin DC-SIGN as the HIV-1 binding factor on DCs, which interacts with the viral envelope glycoproteins. Upon DC maturation, however, DC-SIGN is down-regulated, while HIV-1 capture and trans-infection is strongly enhanced via a glycoprotein-independent capture pathway that recognizes sialyllactose-containing membrane gangliosides. Here we show that the sialic acid-binding Ig-like lectin 1 (Siglec-1, CD169), which is highly expressed on mature DCs, specifically binds HIV-1 and vesicles carrying sialyllactose. Furthermore, Siglec-1 is essential for trans-infection by mature DCs. These findings identify Siglec-1 as a key factor for HIV-1 spread via infectious DC/T-cell synapses, highlighting a novel mechanism that mediates HIV-1 dissemination in activated tissues.

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