Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Nat Commun. 2012;3:1320. doi: 10.1038/ncomms2338.
Retroviruses such as the human immunodeficiency virus, human T-cell lymphotropic virus and murine leukaemia virus are believed to spread via sites of cell-cell contact designated virological synapses. Support for this model is based on in vitro evidence in which infected cells are observed to specifically establish long-lived cell-cell contact with uninfected cells. Whether virological synapses exist in vivo is unknown. Here we apply intravital microscopy to identify a subpopulation of B cells infected with the Friend murine leukaemia virus that form virological synapses with uninfected leucocytes in the lymph node of living mice. In vivo virological synapses are, like their in vitro counterpart, dependent on the expression of the viral envelope glycoprotein and are characterized by a prolonged polarization of viral capsid to the cell-cell interface. Our results validate the concept of virological synapses and introduce intravital imaging as a tool to visualize retroviral spreading directly in living mice.
逆转录病毒,如人类免疫缺陷病毒、人类 T 细胞嗜淋巴细胞病毒和鼠白血病病毒,被认为通过细胞间接触的部位(称为病毒学突触)传播。支持这种模型的依据是体外证据,观察到感染细胞与未感染细胞特异性地建立长期的细胞间接触。病毒学突触是否存在于体内尚不清楚。在这里,我们应用活体显微镜来鉴定一群受 Friend 鼠白血病病毒感染的 B 细胞,这些细胞与活体小鼠淋巴结中的未感染白细胞形成病毒学突触。体内病毒学突触与体外的类似,依赖于病毒包膜糖蛋白的表达,并以病毒衣壳向细胞-细胞界面的长时间极化为特征。我们的结果验证了病毒学突触的概念,并引入活体成像作为一种工具,直接在活体小鼠中可视化逆转录病毒的传播。