Quantitative 3D Video Microscopy of HIV Transfer Across T Cell Virological Synapses

被引:385
作者
Huebner, Wolfgang [1 ]
McNerney, Gregory P. [3 ]
Chen, Ping [1 ]
Dale, Benjamin M. [1 ]
Gordon, Ronald E. [2 ]
Chuang, Frank Y. S. [3 ]
Li, Xiao-Dong [4 ]
Asmuth, David M. [4 ]
Huser, Thomas [3 ,4 ]
Chen, Benjamin K. [1 ]
机构
[1] Mt Sinai Sch Med, Dept Med, Inst Immunol, Div Infect Dis, New York, NY 10029 USA
[2] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA
[3] Univ Calif Davis, NSF Ctr Biophoton Sci & Technol, Sacramento, CA 95817 USA
[4] Univ Calif Davis, Med Ctr, Dept Internal Med, Sacramento, CA 95817 USA
关键词
IMMUNODEFICIENCY-VIRUS TYPE-1; GP41 CYTOPLASMIC TAIL; LYMPHOCYTES; FUSION; SPREAD; ENTRY; CYTOSKELETON; REPLICATION; ENDOCYTOSIS; INFECTION;
D O I
10.1126/science.1167525
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The spread of HIV between immune cells is greatly enhanced by cell-cell adhesions called virological synapses, although the underlying mechanisms have been unclear. With use of an infectious, fluorescent clone of HIV, we tracked the movement of Gag in live CD4 T cells and captured the direct translocation of HIV across the virological synapse. Quantitative, high-speed three-dimensional (3D) video microscopy revealed the rapid formation of micrometer-sized "buttons" containing oligomerized viral Gag protein. Electron microscopy showed that these buttons were packed with budding viral crescents. Viral transfer events were observed to form virus-laden internal compartments within target cells. Continuous time-lapse monitoring showed preferential infection through synapses. Thus, HIV dissemination may be enhanced by virological synapse-mediated cell adhesion coupled to viral endocytosis.
引用
收藏
页码:1743 / 1747
页数:5
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