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.

Worldwide, it is estimated that 34 million people live with human immunodeficiency virus (HIV). In 2010 alone around 2.7 million became newly infected with HIV and 1,8 million died from AIDS. In Canada, it is estimated that 65,000 people are living with HIV/AIDS and thousands are newly infected every year. In the absence of effective vaccines against HIV and with therapies aimed at HIV eradication remaining a far-fetched goal, new approaches to fight HIV infection are warranted. Perhaps new strategies to fight HIV-1 infection could be learned from a group of individuals that remain HIV-1-negative despite being highly exposed to HIV-1. So far it is still not fully understood how these individuals, referred as Highly Exposed to HIV-1 but Persistently Seronegative (HEPS), succeed to avoid HIV-1 transmission. Understanding the basis of their HIV-1 resistance and identifying and characterizing potential anti-HIV-1 molecules, including broadly neutralizing antibodies, from these healthy HIV-1-uninfected-individuals might help direct efforts in next-generation anti-HIV-1 entry inhibitors, vaccine and microbicides design.