New discovery could lead to new methods to block the transmission of HIV

Mar 29 2009

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 human immunodeficiency virus (HIV) from infected to uninfected T cells through structures called virological synapses.

The breakthrough study, which could lead to new methods to block the transmission of HIV, will be published in the March 27 edition of Science.

"Most prior studies of HIV dissemination have focused on free roaming viruses, but this study shows us how direct T cell-to-T cell contact could in fact be the predominant mode of dissemination within the body," said Dr. Benjamin Chen, Assistant Professor of Medicine, Infectious Diseases, Mount Sinai School of Medicine.

"Direct T cell-to-T cell transfer through virological synapses is a highly efficient avenue of HIV infection. Our recent experiments show that the viral structural protein moves with surprising speed in infected cells and that the cell machinery actively participates in the transport of virus between T cells. This suggests there are many targets for interfering with the process," said Dr. Chen.

In order to make the HIV virus visible to track on video from cell to cell, researchers at Mount Sinai created a molecular clone of infectious HIV that contains green fluorescent jellyfish protein. With the team at UC Davis, they then used quantitative, high-speed 3D video microscopy to record both viral particle formation and transmission of the virus between T cells.

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 Dr. Chen. "Future efforts to block HIV transmission may be designed to specifically exploit and block this cell-to-cell mode of infection."