amfAR Grantee’s Movies Catch HIV in the Act
May 2003—How does HIV find the cells it ultimately infects? What kinds of maneuvering must HIV achieve within cells once infection has begun? amfAR grantee Dr. Tom Hope, from the University of Illinois, has developed movie-making technology that has the potential to answer these questions. “We will visualize the entire HIV life cycle,” Dr. Hope said, adding that his technology may help to solve many of the remaining enigmas surrounding the virus. As he said, “If a picture is worth a thousand words, then a movie is worth a million.”
Dr. Tom Hope
Dr. Hope’s new technology allows him to catch HIV in the act. First, fluorescent tags are attached to the virus and to the cells with which it interacts. A mix of virus and cells is then placed in a dish and filmed under the microscope. Dr. Hope and his team can visualize HIV as it attaches to dendritic cells—immune cells that are believed to play a crucial role in bringing the virus into contact with T cells, the ultimate targets for infection. The dendritic cells are thought to be especially important in enhancing sexual transmission of the virus.
The virus, shown in green, concentrates to the point of contact between a dendritic cell (top) and a T cell (bottom).
A paper from Dr. Hope’s lab, published recently in the prestigious journal Science, shows the attachment of HIV to dendritic cells and the subsequent presentation of the virus by those dendritic cells to target cells, through a series of fluorescent images (see image above).
HIV appears to be subverting a fundamental characteristic of dendritic cells—seeking out invading pathogens, like viruses, and transporting them to the lymph nodes for destruction by an orchestrated response of T and B immune cells. For HIV, however, this is the ideal scenario—instead of being destroyed in the lymph nodes, HIV takes advantage of its proximity to its target and infects T cells before it can be killed.
Moreover, when dendritic cells carrying the virus make contact with T cells, the HIV that had been widely dispersed throughout the dendritic cell moves towards the site of contact with the T cell. At the same time, the receptors on the T cell required for HIV infection also move to the site of contact. “What this is effectively doing is concentrating the components that are needed [quote1]for HIV to infect the cell,” Dr. Hope said. “One of the interesting things about this whole system is, the less virus you have, the greater the influence of the dendritic cells.” In other words, in cases where there is so little virus present that infection would probably not take place, the dendritic cells concentrate much of the virus into one place while bringing it directly to those cells HIV infects.
How does Dr. Hope feel about his research? “It’s really fun to look at things. You get to see what’s happening, and that’s pretty insightful.”