Ménager Mickaël M, Littman Dan R
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Howard Hughes Medical Institute.
Cell. 2016 Feb 11;164(4):695-709. doi: 10.1016/j.cell.2015.12.036. Epub 2016 Jan 28.
Whereas human dendritic cells (DCs) are largely resistant to productive infection with HIV-1, they have a unique ability to take up the virus and transmit it efficiently to T lymphocytes through a process of trans-infection or trans-enhancement. To elucidate the molecular and cell biological mechanism for trans-enhancement, we performed an shRNA screen of several hundred genes involved in organelle and membrane trafficking in immature human monocyte-derived dendritic cells (MDDCs). We identified TSPAN7 and DNM2, which control actin nucleation and stabilization, as having important and distinct roles in limiting HIV-1 endocytosis and in maintaining virus particles on dendrites, which is required for efficient transfer to T lymphocytes. Further characterization of this process may provide insights not only into the role of DCs in transmission and dissemination of HIV-1 but also more broadly into mechanisms controlling capture and internalization of pathogens.
虽然人类树突状细胞（DCs）对HIV-1的有效感染具有很大的抗性，但它们具有独特的能力，能够摄取病毒并通过转染或转增强过程将其有效地传递给T淋巴细胞。为了阐明转增强的分子和细胞生物学机制，我们对未成熟的人类单核细胞衍生树突状细胞（MDDCs）中参与细胞器和膜运输的数百个基因进行了shRNA筛选。我们鉴定出TSPAN7和DNM2，它们控制肌动蛋白的成核和稳定，在限制HIV-1内吞作用以及在维持树突上的病毒颗粒方面具有重要且不同的作用，而这是有效转移到T淋巴细胞所必需的。对这一过程的进一步表征不仅可能为DCs在HIV-1传播和扩散中的作用提供见解，而且更广泛地为控制病原体捕获和内化的机制提供见解。
