Scientists Use Molecular Can Opener to Target HIV

One of the main roadblocks that have stymied researchers’ attempts at generating an effective HIV vaccine is somehow managing to get antibodies and other immune cells to attack the appropriate targets that are practically hermetically sealed within the virus.

However, scientists at the Montreal University Health Centre (CHUM) believe they have found what amounts to a molecular can opener, forcing the virus to open up and expose its vulnerable parts to the host immune system, ultimately leading to viral clearance. The researchers are optimistic that this approach could also be part of the solution for one day eradicating the virus.   

“We found that people infected with the HIV-1 virus have naturally occurring antibodies that have the potential to kill the infected cells,” explained Andrés Finzi, Ph.D., research assistant professor at the University of Montreal and senior author on the current study. “We just have to give them a little push by adding a tiny molecule that acts as a can opener to force the viral envelope to expose regions recognized by the antibodies, which forms a bridge with some cells of the immune system, initiating the attack.”

The findings from this study were published recently in PNAS through an article entitled “CD4 mimetics sensitize HIV-1-infected cells to ADCC.”

Dr. Finzi and his colleagues used a CD4 mimetic compound called JP-III-48, which mimics the surface of a T cell and induces the CD4 bound confirmation of the HIV virus. This conformational change in turn causes the virus to expose antigens that are typically hidden from the host immune system.    

“The virus has to get rid of the CD4 proteins to protect itself,” stated Jonathan Richard, Ph.D., postdoctoral researcher at CHUM and lead author on the study. “Adding the small molecule forces the viral envelop to open, like a flower. The antibodies that are naturally present after the infection can then target the infected cells so they are killed by the immune system.”

Additionally, for several years scientists have been trying to devise a vaccine to block HIV infection. While antiretroviral drugs can slow the progression of the disease, the virus can often lie dormant in cells and reemerge at some point in the future—the so called HIV reservoirs.

“The solution is to develop a ‘shock and kill’ therapy,” said Dr. Finzi. “We have to reactivate HIV reservoirs to force the virus out of its hiding place, and then kill the infected cells with this molecule and the already present antibodies,”

Dr. Finzi and his colleagues are enthusiastic about their findings and feel that CD4 mimetics represent an attractive approach to prevent and control HIV-1 infections. The researchers are currently taking their method to the next phase by designing experiments to treat HIV infected primates.