Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages remains elusive. Here, we demonstrate that fusion of infected CD4+ T lymphocytes with human macrophages leads to their efficient and productive infection. Importantly, several tissue macrophage populations undergo this heterotypic cell fusion, including synovial, placental, lung alveolar, and tonsil macrophages. We also find that this mode of infection is modulated by the macrophage polarization state. This fusion process engages a specific short-lived adhesion structure and is controlled by the CD81 tetraspanin, which activates RhoA/ROCK-dependent actomyosin contractility in macrophages. Our study provides important insights into the mechanisms underlying infection of tissue-resident macrophages, and establishment of persistent cellular reservoirs in patients.

中文翻译：

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通过与受感染的 CD4+ T 细胞融合而产生组织巨噬细胞的 HIV-1 感染

巨噬细胞对于 HIV-1 发病机制至关重要，是主要的病毒库。因此，了解巨噬细胞的感染至关重要，特别是组织巨噬细胞，它们在体内广泛感染，但很少允许无细胞感染。尽管HIV-1的细胞间传播是体内巨噬细胞感染的决定性模式，但HIV-1如何向巨噬细胞转移仍然难以捉摸。在这里，我们证明受感染的 CD4+ T 淋巴细胞与人类巨噬细胞的融合导致其有效且富有成效的感染。重要的是，一些组织巨噬细胞群经历这种异型细胞融合，包括滑膜、胎盘、肺泡和扁桃体巨噬细胞。我们还发现这种感染模式是由巨噬细胞极化状态调节的。这种融合过程涉及特定的短命粘附结构，并由 CD81 四跨膜蛋白控制，它激活巨噬细胞中 RhoA/ROCK 依赖性肌动球蛋白收缩性。我们的研究为了解组织驻留巨噬细胞感染的机制以及患者体内持久细胞储存库的建立提供了重要的见解。