Grant: Operating Grant - PA: CHVI Vaccine Discovery and Social Research

In the absence of treatment, human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), which has already killed more than 34 million people worldwide. To be able to spread, HIV needs first to enter human cells. To do so, HIV has developed a unique key (envelope glycoproteins, gp120 and gp41) that recognizes a particular lock (receptor CD4 and coreceptors CCR5 or CXCR4) in human cells (mainly lymphocytes T CD4 and macrophages). This key needs to move into the lock (conformational changes of gp120 and gp41) to allow viral entry. In the absence of no effective vaccines against HIV and with therapies aimed at HIV eradication remaining a far fetched goal, new ways to fight HIV infection are warranted. Our preliminary results indicate that antibodies recognizing this key in presence of the receptor CD4 are able to recruit cells from the immune system to eliminate HIV-1-infected cells through a mechanism known as Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC). However, little is known about how this happens and how the virus tries to evade from this response. This proposal will advance our understanding of what could be a critical mechanism required for elimination of HIV-1-infected cells and has the potential to develop new inhibitors or immunogens against the key of HIV.