Baxter Amy E, Russell Rebecca A, Duncan Christopher J A, Moore Michael D, Willberg Christian B, Pablos Jose L, Finzi Andrés, Kaufmann Daniel E, Ochsenbauer Christina, Kappes John C, Groot Fedde, Sattentau Quentin J
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK; Department of Medicine, Université de Montréal, Montreal, Quebec, H2X 0A9, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Université de Montréal, Montreal, Quebec, H2X 0A9, Canada.
The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Cell Host Microbe. 2014 Dec 10;16(6):711-21. doi: 10.1016/j.chom.2014.10.010. Epub 2014 Nov 20.
Macrophages contribute to HIV-1 pathogenesis by forming a viral reservoir and mediating neurological disorders. Cell-free HIV-1 infection of macrophages is inefficient, in part due to low plasma membrane expression of viral entry receptors. We find that macrophages selectively capture and engulf HIV-1-infected CD4+ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. Macrophages infected by this cell-to-cell route were highly permissive for both CCR5-using macrophage-tropic and otherwise weakly macrophage-tropic transmitted/founder viruses but restrictive for nonmacrophage-tropic CXCR4-using virus. These results have implications for establishment of the macrophage reservoir and HIV-1 dissemination in vivo.
巨噬细胞通过形成病毒储存库和介导神经紊乱来促进HIV-1发病机制。巨噬细胞的无细胞HIV-1感染效率低下，部分原因是病毒进入受体的质膜表达水平较低。我们发现巨噬细胞选择性地捕获并吞噬受HIV-1感染的CD4+ T细胞，从而导致巨噬细胞有效感染。无论是健康的还是死亡或濒死的受感染T细胞，都是通过不依赖病毒包膜糖蛋白-受体的相互作用被摄取的，这意味着一种不同于传统病毒学突触形成的机制。通过这种细胞间途径感染的巨噬细胞对使用CCR5的巨噬细胞嗜性病毒以及其他弱巨噬细胞嗜性的传播/奠基病毒具有高度易感性，但对使用CXCR4的非巨噬细胞嗜性病毒具有限制性。这些结果对体内巨噬细胞储存库的建立和HIV-1传播具有重要意义。
