Secondary lymphoid organ fibroblastic reticular cells mediate trans-infection of HIV-1 via CD44-hyaluronan interactions.
Secondary lymphoid organ fibroblastic reticular cells mediate trans-infection of HIV-1 via CD44-hyaluronan interactions.
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DOI：
10.1038/s41467-018-04846-w
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发表时间：
2018-06-22
影响因子：
16.6
通讯作者：
Ono A
中科院分区：
文献类型：
--
作者：
Murakami T;Kim J;Li Y;Green GE;Shikanov A;Ono A
成纤维细胞网状细胞(FRC)是次级淋巴器官中的基质细胞，是HIV-1感染CD4+T细胞的主要部位。尽管FRC调节T细胞的存活、增殖和迁移，但它们在HIV-1传播中是否起到任何作用还没有研究。在这里，我们表明，FRC通过转基因感染增强HIV-1的传播，其中FRC捕获HIV-1，并促进与FRC接触的T细胞的感染。在二维和三维培养系统中，FRCS以依赖于病毒产生细胞的方式介导反式感染。这种产生细胞的依赖性，也观察到病毒在体外次级淋巴组织中的传播，这是由CD44结合到病毒颗粒中和透明质酸结合到CD44分子中所解释的。这种病毒相关的透明质酸与FRC上表达的CD44相互作用，从而促进FRC捕获病毒。总体而言，我们的结果揭示了FRC在促进HIV-1传播方面的新作用。成纤维细胞网状细胞(FRC)是T细胞在次级淋巴器官中存活、增殖和迁移的重要调节因子，但其在HIV感染中的作用尚未被研究。在这里，村上等人。显示FRC通过CD44和透明质酸介导的反式感染增强艾滋病毒的传播。
Fibroblastic reticular cells (FRCs) are stromal cells in secondary lymphoid organs, the major sites for HIV-1 infection of CD4+ T cells. Although FRCs regulate T cell survival, proliferation, and migration, whether they play any role in HIV-1 spread has not been studied. Here, we show that FRCs enhance HIV-1 spread via trans-infection in which FRCs capture HIV-1 and facilitate infection of T cells that come into contact with FRCs. FRCs mediate trans-infection in both two- and three-dimensional culture systems and in a manner dependent on the virus producer cells. This producer cell dependence, which was also observed for virus spread in secondary lymphoid tissues ex vivo, is accounted for by CD44 incorporated into virus particles and hyaluronan bound to such CD44 molecules. This virus-associated hyaluronan interacts with CD44 expressed on FRCs, thereby promoting virus capture by FRCs. Overall, our results reveal a novel role for FRCs in promoting HIV-1 spread. Fibroblastic reticular cells (FRCs) are important regulators of T cell survival, proliferation, and migration in secondary lymphoid organs, but their role in HIV infection isn’t studied. Here, Murakami et al. show that FRCs enhance HIV spread via CD44- and hyaluronan-mediated trans-infection.