The Role of DDX5 and DDX17 in the HIV-1 Life Cycle. (360G-Wellcome-097223_Z_11_Z)

HIV/AIDS has already, infected approximately 40 million people, and killed 20 million. Antiviral treatment is good however the virus mutates to evade both drugs and the human immune response. In Professor Lever's lab the interaction of the virus with the cell is studied and in particular how the virus uses cell factors to help assemble itself and export new viruses.The role of cellular RNA helicases in trafficking viral RNA through the cell has recently been under study and by extensive screenin g, DDX5 and DDX17 appear to be important candidates which have not previously been identified as involved in HIV infection.This study aims to assess their contribution. Since cellular proteins will not undergo mutational escape the parts of the viral RNA interacting with them must also be highly conserved and thus more vulnerable to therapeutic intervention. I plan to use a series of cell biological, biochemical, molecular biological and imaging techniques to confirm these findings and establish the specific stage of the virus lifecycle which is affected by knockdown of these proteins, and to evaluate where the interaction occurs within the cell. Ultimately, in collaboration with the Department of Chemistry, we aim to use small chemical substances to inhibit these interactions.