The goal of this project was to develop a single-molecular complex approach to study the mechanisms of cell entry of the Human Immunodeficiency Virus (HIV), which remains one of the world’s most serious health threats. As an enveloped virus, HIV transfers its genome into a cell by fusion of the viral membrane with the target cell membrane. This process is promoted by a complex series of conformational changes in the HIV envelope (Env) glycoprotein, induced by CD4–gp120–coreceptor interactions and resulted in bringing the viral and cell membranes into a close contact, inducing membrane fusion. We used two mechanical-based assays developed in the Zhu lab to quantify the kinetics of CD4/coreceptor binding and conformational changes in Env.
Two specific aims were:
1. Characterize the interactions of Env with CD4 and coreceptors
2. Observe the conformational changes in Env en route to membrane fusion
Due to technical challenges related to Aim 2, we primarily focused on Aim1 and obtained novel results related to the cooperativity and strength of Env-receptor and Env-receptor/coreceptor binding.