HIV Virology Core To support the needs of the three PCHPI projects, recipients of Collaborative Development Awards, and external collaborative projects, we will establish an HIV Virology Core (HVC). The primary missons of the HVC will be to test hypotheses resulting from new structural information generated by the center projects and to drive studies that are complementary to the proposed structural work, as detailed in the project descriptions. The HVC will achieve these goals by performing functional studies of HIV-1 using a battery of assays and tools of the trade. Three groups, led by experienced investigators, will contribute to the effort: Chris Aiken (specializing in assays of HIV-1 replication; purification and analysis of HIV-1 cores; functional studies of HIV-1 mutants; and assays of endogenous reverse transcription); Alan Engelman (specializing in functional studies of HIV-1 integration, including deep sequencing analysis of integration sites; gene knock-out and recoding knock-in experiments to anlyze effects of cell mutations on HIV-1 infection, with an emphasis on nuclear entry and integration defects; quantitative assessment of virion morphology by transmission electron microscopy; and work with primary human cell cultures); and Zandrea Ambrose (specializing in single-cycle infection assays; in vitro analysis of single-particle uncoating; staging of HIV-1 infection defects; and cell-based imaging studies of HIV-1 ingress, including intracellular trafficking, gene knockdown/knockout of trafficking proteins, and infections of primary cells). The HVC will be collaboratively managed by Aiken and Engelman, an arrangement that has served the PCHPI well and will ensure that the Projects are appropriately supported.