Analysis of the human immnunodeficiency virus budding site

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Human immunodeficiency virus (HIV) type 1 is assembled as immature, non-infectious particle which undergoes extracellular maturation to the infectious virion. Virus assembly occurs concomitant with envelopment at the plasma membrane of the infected cell. Particle formation is mediated by the viral Gag polyprotein, is presumed to take place at lipid rafts, and requires the action of cellular E S CRT-machinery to facilitate release of the budding virion. In this project, we plan to determine the structure of the HIV-1 budding site and of budding-arrested particles by cryo-electron tomography together with the group of K, Grünewald (MPI Martinsried). In addition, we will analyze the contribution of the conical actin layer to HIV-1 budding using a combination of biochemical and ultrastructural approaches and treatment with F-actin stabilizing and destabilizing drugs. Lastly, we will examine the contribution of lipid rafts, specific lipids and of protein phosphorylation to HIV-1 particle formation. These studies should lead to a detailed structural and molecular understanding of the HIV-1 budding site and may aid in the search for new strategies for antiviral therapy.