Quantitative 3D video microscopy of HIV transfer across T cell virological synapses.
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.
Hübner
Wolfgang
W
Division of Infectious Diseases, Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
McNerney
Gregory P
GP
Chen
Ping
P
Dale
Benjamin M
BM
Gordon
Ronald E
RE
Chuang
Frank Y S
FY
Li
Xiao-Dong
XD
Asmuth
David M
DM
Huser
Thomas
T
Chen
Benjamin K
BK