For the first time, researchers filmed the transfer of HIV
from infected to uninfected T cells through structures called virological
synapses. The study, conducted by researchers at Mount Sinai
School of Medicine, in New York, NY, and the Center for Biophotonics Science and Technology, University of California,
Davis, could lead to new methods to block the transmission of HIV. The study published
in the March 27 edition of Science.
Researchers captured the video, shown below, by creating a
molecular clone of infectious HIV that contains green fluorescent protein. They
then used quantitative, high-speed 3-D video microscopy to
record both viral particle formation and transmission of the virus between T
cells.
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The resulting images and videos show that, once an infected cell
adheres to a healthy cell, the HIV proteins–which appear bright green in the
study–migrate within minutes to the contact site. At that point, large
packets of virus are simultaneously released by the infected cell and
internalized by the recipient cell. This efficient mode of transfer is a
distinct pathway from the cell-free infection that has been the focus of most
prior HIV studies, and reveals another mechanism by which the virus evades
immune responses that can neutralize free virus particles within the body.
“We found that the transfer of HIV is highly coordinated between T
cells, and that the transfer is rapid and massive,” said [Benjamin] Chen, [assistant professor
of medicine, infectious diseases, Mount Sinai School of Medicine].”Future efforts
to block HIV transmission may be designed to specifically exploit and block
this cell-to-cell mode of infection.”
A rotating three-dimensional view of an HIV-infected T cell (green) forming virological synapses with three healthy CD4+ cells (red). The viral structural protein, shown in green, accumulates in button-shaped structures at the contact sites.
This movie shows high-speed imaging of HIV transfer across a virological synapse. The video begins with a still view of two T cells with transmitted light and an outline of a spot where a synaptic button has formed between them. The movie then shows the movement of fluorescent viral protein into the synaptic button, followed by the transfer of material from the button into the target cells. Note that the movie focuses on the movement of the viral protein without indicating the outlines of the recipient cell.
The video shows a cell that has engaged in a synapse becoming infected days later. Infection was captured by continuous long-term imaging over three days. The HIV green fluorescence image is presented on the left while an overlay of green fluorescence and bright field image is shown on the right. Images were acquired every 10 minutes over 67 hours.
