Tiny molecule that outsmarts HIV identified

In a breakthrough, scientists have identified a tiny molecule that forces the HIV virus to open up and expose its vulnerable parts, allowing the immune system to kill the infected body cells.

The finding opens a new path in the fight against HIV and could ultimately lead to the design of a vaccine to prevent transmission of the virus, researchers said.

This innovative approach could also be part of the solution for eradicating the virus. Despite recent advances, 35 million people are infected with HIV-1 worldwide, they said.
"We found that people infected with the HIV-1 virus have naturally occurring antibodies that have the potential to kill the infected cells," said study lead author Andres Finzi, professor at the University of Montreal.

"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 recognised by the antibodies, which forms a bridge with some cells of the immune system, initiating the attack," said Finzi.

In an earlier study, the same researchers showed that the serum of patients infected with HIV-1 facilitated the elimination of infected cells when two proteins specific to the virus, Nef and Vpu, were deactivated by gene mutation.

In real life, however, wild-type HIV-1 virus, responsible for the vast majority of infections in the world, still contains these proteins, which act like bodyguards.

We can outwit these proteins by adding a tiny molecule to the cell surfaces of infected patients – called JP-III-48 – which imitates a protein called CD4.

CD4 proteins are located at the surface of T lymphocytes and allow immune system cells to be infected by HIV.

"The virus has to get rid of the CD4 proteins to protect itself. Adding the small molecule forces the viral envelop to open, like a flower" said Jonathan Richard, postdoctoral researcher at the CRCHUM and lead author of the study.

"The antibodies that are naturally present after the infection can then target the infected cells so they are killed by the immune system," said Richard.

The JP-III-48 molecule was developed by researchers at Harvard University and the University of Pennsylvania; however, this is the first time it has been successfully tested on patients infected with HIV.

The discovery could help develop a two-part vaccine to prevent HIV infection: through antibodies that are easy to generate and using this new family of molecules, researchers said.The research was published in the journal PNAS.