"Can Opener" Molecule Makes HIV Vulnerable to Attack

A molecule that mimics a particular kind of protein has been demonstrated by a new study to render HIV vulnerable to antibodies that could kill off infected cells.

The JP-III-48 molecule forces HIV to open up and expose regions that are vulnerable to attack from the immune system.

Researchers from the Centre hospitalier de l'Université de Montréal (CHUM) Research Centre in Canada have described the molecule in question, JP-III-48, as acting like a "can opener" due to the way that it forces the human immunodeficiency virus (HIV) to open up and expose its vulnerable parts.

The researchers at the University of Montreal, state the team also found that people infected with HIV-1 virus have naturally occurring antibodies with the potential to kill infected cells.

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 development of a vaccine to prevent HIV infection has long been a goal of researchers. At present, antiretroviral drugs are used to slow the virus down but they are unable to prevent the formation of HIV "reservoirs" - areas where the virus remains hidden and dormant within cells. As soon as antiretroviral treatment ends, the virus returns.

Worldwide, around 35 million people are estimated to be infected with HIV-1, the predominant form of the virus. It is hoped that this new discovery could lead toward the development of a vaccine to finally stop the spread of HIV.

'Shock and kill' therapy may be the key to future HIV treatment

Previous research published earlier this year demonstrated that cells infected with HIV-1 were more easily eliminated when two HIV-specific proteins, Nef and Vpu, were deactivated by gene mutation.

This finding formed the basis of the new study, published in Proceedings of the National Academy of Sciences. These two proteins protect the virus from attack. If these proteins could be overcome, the virus becomes vulnerable.

The researchers added the JP-III-48 molecule to the surfaces of cells infected with HIV. This molecule imitates a protein called CD4 which is often found on the surface of white blood cells called T lymphocytes. CD4 proteins make these white blood cells vulnerable to HIV infection.

The research team explains how the introduction of JP-III-48 subsequently makes infected cells vulnerable to attack:

"The virus has to get rid of the CD4 proteins to protect itself. Adding the small molecule forces the viral envelope 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."

JP-III-48 was previously developed by researchers from Harvard University and the University of Pennsylvania. This study marks the first time the molecule has been tested successfully on patients with HIV.

Then researchers believe that the molecule could be used as part of a treatment to eliminate the HIV reservoirs of people infected with the virus. The solution is to develop a 'shock and kill' therapy. We have to reactivate HIV reservoirs to force the virus out of its hiding place, then kill the infected cells with this molecule and the already present antibodies.

The molecule could also be potentially used as a component in a two-part vaccine, alongside antibodies to target the virus. The next step for the team is to assess JP-III-48 capabilities in tests involving monkeys.

References:

1.  CD4 mimetics sensitize HIV-1-infected cells to ADCC, Jonathan Richard, et al., Proceedings of the National Academy of Sciences, doi: 10.1073/pnas.1506755112, published online 5 May 2015, abstract.
2.  Université de Montréal news release, accessed 5 May 2015 via Newswise.