PLoS Biology：艾滋病病毒扩散机理被破解

ipsvirus

原帖由 ipsvirus 2012-5-17 19:16发表于老论坛


4月24日，来自巴塞罗那Irsi Caixa艾滋病研究所的科学家向媒体公布，他们破解了艾滋病病毒（HIV）扩散、渗透直至颠覆免疫系统全过程的分子生物学机理，该研究成果已发表在当日出版的美国科学公共图书馆生物期刊《PLoS Biology》上。

研究人员发现，艾滋病病毒外壳表面的神经节苷酯分子是使病毒侵入人体树突状细胞、进而在体内传播的“帮凶”。进一步实验证实，构造相似但不含这种分子的人造病毒样颗粒无法进入树突状细胞。他们据此认为，去除神经节苷酯将有效抑制艾滋病病毒扩散。

树突状细胞平日在人体各组织内“巡逻”，捕捉病原体“入侵者”并将其粉碎，把“样本”送入淋巴组织，启动相关免疫反应。但对于艾滋病病毒，由于神经节苷酯的存在，树突状细胞无法将其分割，因此病毒得以完整侵入免疫系统，这等于给免疫系统放置了一个允许艾滋病病毒自由出入的“特洛伊木马”。经由树突状细胞的运送，HIV病毒进入淋巴结摧毁T CD4淋巴细胞，从而导致了机体免疫功能的丧失。

基于上述研究成果，科学家们表示，他们将锁定“去除神经节苷酯分子，切断HIV病毒在体内扩散的渠道”这一目标，加紧进行生物医药研发，为人类攻克艾滋病探索和开辟出一条新路。

ipsvirus

Sialyllactose in Viral Membrane Gangliosides Is a Novel Molecular Recognition Pattern for Mature Dendritic Cell Capture of HIV-1

Nuria Izquierdo-Useros, Maier Lorizate, F.-Xabier Contreras, Maria T. Rodriguez-Plata, Bärbel Glass, Itziar Erkizia, Julia G. Prado, Josefina Casas, Gemma Fabriàs, Hans-Georg Kräusslich, Javier Martinez-Picado

HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4+ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1.