The main theme of my research career is centered broadly in the field of structural biology and biochemistry of retroviruses. High resolution NMR and other biophysical methods will be employed to study interactions between viral proteins and cellular constituents. Knowledge of the mechanistic functions by which viral proteins recognize cellular factors might enable a novel targeting of therapeutics to prevent the replication of HIV and other viruses.
The first project will be focused on understanding how the interactions between HIV-1 Gag and Annexin 2 (Anx2) promote virus assembly. Anx2 is a 35 KDa endosomal protein involved in vesicular trafficking and formation, endocytosis and exocytosis, and recently has been identified as a novel HIV-1 Gag binding partner in macrophages. Depletion of Anx2 during monocyte-derived macrophages (MDM) infection causes a decrease in virus production and a defect in maturation and infectivity in the released virions.
The aim of the second project is to understand how the viral infectivity factor protein (Vif) of HIV-1 functions to counteract the anti-retroviral cellular factor APOlipoprotein B mRNA-editing Enzyme-Catalytic polypeptide-like 3G (APOBEC3G) during viral replication. HIV-1 Vif is essential for promoting efficient viral replication in vivo, and recent evidence has demonstrated that Vif neutralizes a potent intracellular defense pathway that protects mammals from retroviruses that invade their genomes. APOBEC3G is a critical component of this pathway, which lethally hypermutates the retroviral genome, triggering its degradation.
