Diaz-Griffero Lab

The restriction factor MxB is an interferon-a inducible protein that blocks HIV-1 infection in T cells (Goujon et al., 2013; Kane et al., 2013; Liu et al., 2013). Our investigations revealed that MxB blocks HIV-1 infection by inhibiting the uncoating process of HIV-1(Fricke et al., 2014)(Fig. 4). We found that MxB directly interacts with the HIV-1 core by using a triple arginine in the N-terminal domain of MxB (Schulte et al., 2015). Our studies also showed that oligomerization of MxB is essential for the ability of MxB to bind to the HIV-1 core and restrict HIV-1(Buffone et al., 2015). Overall, these results suggested that MxB binding to the core is forming an array on the surface of the HIV-1 core. Future experiments will test the hypothesis that MxB forms an array of protein on the surface of the HIV-1 core, which leads to inhibition of uncoating. To this end, we will perform Electron Microscopy of pure MxB protein overlaid on in vitro assembled HIV-1 CA that forms flat sheets. These experiments will show whether MxB cages the HIV-1 core in order to prevent HIV-1 uncoating. We are currently testing our purified MxB protein from human cells for its ability to interact with HIV-1 cores.