Project Leader: Robert Stroud
Like Vif, Vpu targets host restriction factors for degradation. HIV assembly intimately involves host cell membranes and membrane proteins but major gaps in knowledge remain about the mechanisms and structures of these viral-host interactions. The transmembrane viral protein U (Vpu) is expressed late in the viral life cycle and interferes with host proteins that otherwise restrict virus particle release. Vpu interacts with many proteins in the cell, including tetherin/BST2, CD4, CD1b, NTB-A, and CD40, and acts to degrade or internalize these surface molecules by contacting bTRCP:SCF E3 ligase and adaptor protein 2 (AP2). The HARC Center Proteomics/Genomics Core identified 55 other host factors that either directly interact with Vpu or associate with host-Vpu-host protein complexes. These partners provide additional candidates for host restriction factors and targets for degradation. The Vpu project headed by Bob Stroud is aimed at exploring these interactions at a mechanistic and structural level.