Nobile Cinzia, Moris Arnaud, Porrot Françoise, Sol-Foulon Nathalie, Schwartz Olivier
Virus and Immunity Group, URA CNRS 1930, Institut Pasteur, 75724 Paris Cedex 15, France.
J Virol. 2003 May;77(9):5313-23. doi: 10.1128/jvi.77.9.5313-5323.2003.
DC-SIGN, a lectin expressed on dendritic cell and macrophage subsets, binds to human immunodeficiency virus Env glycoproteins, allowing capture of viral particles. Captured virions either infect target cells or are efficiently transmitted to lymphocytes. Cellular mechanisms underlying the effects of DC-SIGN remain poorly understood. Here we have analyzed the effects of DC-SIGN on viral entry and on syncytium formation induced by Env glycoproteins. The lectin enhanced susceptibility to viral infection and dramatically increased virion internalization. Captured virions accumulated in the vesicular pathway, and their access to the cytosol was altered. Strikingly, the presence of DC-SIGN on target cells inhibited their ability to form syncytia with Env-expressing cells. However, increasing CD4 surface levels on target cells alleviated this inhibitory effect of DC-SIGN. Moreover, the potency of the viral fusion inhibitor T-20 was not affected in DC-SIGN-expressing cells. Altogether, our results indicate that DC-SIGN exerts subtle and complex effects during early steps of HIV type 1 replication. DC-SIGN facilitates capture and accumulation of viral particles in a vesicular compartment and inhibits viral fusion. Competition between CD4 and DC-SIGN for Env binding likely affects virus access to the cytosol and syncytium formation.
DC-SIGN是一种在树突状细胞和巨噬细胞亚群上表达的凝集素，它能与人免疫缺陷病毒Env糖蛋白结合，从而捕获病毒颗粒。被捕获的病毒粒子要么感染靶细胞，要么被有效地传递给淋巴细胞。DC-SIGN作用的细胞机制仍知之甚少。在此，我们分析了DC-SIGN对病毒进入以及Env糖蛋白诱导的合胞体形成的影响。这种凝集素增强了对病毒感染的易感性，并显著增加了病毒粒子的内化。被捕获的病毒粒子在囊泡途径中积累，并且它们进入细胞质的途径发生了改变。引人注目的是，靶细胞上DC-SIGN的存在抑制了它们与表达Env的细胞形成合胞体的能力。然而，增加靶细胞表面的CD4水平可减轻DC-SIGN的这种抑制作用。此外，病毒融合抑制剂T-20在表达DC-SIGN的细胞中的效力不受影响。总之，我们的结果表明，DC-SIGN在1型人类免疫缺陷病毒复制的早期阶段发挥着微妙而复杂的作用。DC-SIGN促进病毒粒子在囊泡区室中的捕获和积累，并抑制病毒融合。CD4和DC-SIGN对Env结合的竞争可能影响病毒进入细胞质和合胞体的形成。
