Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Virology. 2011 Jan 20;409(2):234-50. doi: 10.1016/j.virol.2010.10.018. Epub 2010 Nov 6.
Recent studies provide compelling evidence that HIV-1 entry in cell lines and lymphocytes proceeds by endocytosis, but these studies are still lacking in macrophages, an important natural target cell for HIV-1. Macrophages exhibit continual and extensive endocytic activity as part of their natural functions, so we investigated the uptake pathways involved in productive HIV-1 entry. We find that caveolae are not utilised by HIV-1, because the main structural proteins, caveolin-1 and 2 are absent from most human leukocytes. We then focused on macropinocytosis; we find that HIV-1 entry into macrophages is sensitive to inhibitors of Na(+)/H(+) exchange, actin rearrangement, dynamin, Rho family GTPases, and Pak1, but not to inhibitors of PI-3 kinase and myosin II. This leads us to conclude that HIV entry into macrophages proceeds by an endocytic pathway that is not classical macropinocytosis. Because of the limitations of a purely pharmacological study such as this, the final elucidation of this pathway awaits the development of reliable forward genetic approaches in authentic macrophages.
最近的研究提供了令人信服的证据表明，HIV-1 进入细胞系和淋巴细胞是通过内吞作用进行的，但这些研究在巨噬细胞中仍然缺乏，巨噬细胞是 HIV-1 的一个重要天然靶细胞。巨噬细胞表现出持续和广泛的内吞作用，作为其天然功能的一部分，因此我们研究了参与 HIV-1 有效进入的摄取途径。我们发现 HIV-1 不利用小窝，因为主要结构蛋白 caveolin-1 和 2 不存在于大多数人白细胞中。然后我们专注于巨胞饮作用；我们发现 HIV-1 进入巨噬细胞对 Na(+)/H(+)交换、肌动蛋白重排、胞质分裂蛋白、Rho 家族 GTP 酶和 Pak1 的抑制剂敏感，但对 PI-3 激酶和肌球蛋白 II 的抑制剂不敏感。这使我们得出结论，HIV 进入巨噬细胞是通过一种非经典巨胞饮作用的内吞途径进行的。由于这种纯粹的药理学研究存在局限性，因此该途径的最终阐明有待于在真正的巨噬细胞中开发可靠的正向遗传方法。
