While historically, studies of human immunodeficiency virus (HIV) dissemination have focused on free roaming viruses, a team of researchers at
Mount Sinai School of Medicine and the
UC Davis Center for Biophotonics Science and Technology have for the first time captured on video the transfer of the virus from infected to uninfected T cells through structures called virological synapses. According to the researchers, the breakthrough study could one day lead to the development of new methods to block transmission of the deadly virus.
Publishing their findings last month in the journal
Science, the team from Mount Sinai created a molecular close of infectious HIV that contains green fluorescent jellyfish protein and observed as the virus moved from one cell to another. Meanwhile, the team at UC Davis used quantitative, high-speed 3D video microscopy to record both viral particle formation and transmission of the virus between T cells. The video, shown here with permission from Science, showed that, once the infected cell adhered to a healthy cell, the HIV proteins – which appear bright green on the video – migrated within minutes to the contact site. At that point, large packets of virus were 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, says Dr. Benjamin Chen, assistant professor of Medicine, Infectious Diseases at Mount Sinai and one of the lead authors on the study.
"We found that the transfer of HIV is highly coordinated between T cells, and that the transfer is rapid and massive," said Chen says. "This is not a concept that is foreign to virologists, but HIV had not really been appreciated as entering this way. The discovery of these pathways is surprising, and our findings offer new targets for thinking about how we can inhibit the transfer process."
While future efforts to block HIV transmission may be designed to specifically exploit and block this cell-to-cell mode of infection, Chen cautions that these theories have only just begun to take shape.
"One idea we plan to pursue is to study the molecular mechanisms supporting entry through this particular pathway and try to better define the proteins and cell compartments which are involved," Chen says. "Another important area of future study is vaccine development and how this might influence HIV transfer as well."
Chen says that while the researchers are not actively seeking commercial partners at this time, they have engaged in some early discussions with interested parties in Big Pharma.
"This discovery has also been very visually rewarding in that it tells a story that is very compelling because of the movie that is attached to it," Chen says. "It allows people to get a very intuitive sense of our findings, and some of the comments we have received on the Web have been very receptive and interesting."
Additional videos from the study are available at
http://www.youtube.com/user/GreenVSLab.
