The Spearman laboratory focuses on HIV assembly, host restriction factors that limit HIV replication, and the development of novel HIV vaccines. HIV assembly is directed by the Gag protein and occurs primarily on the plasma membrane of infected cells. Current projects in HIV assembly are focused on identifying trafficking factors that direct Gag and Env to the particle assembly site, and on defining the nature of the intracellular virus-containing compartment in human macrophages. A new pathway directing HIV Env to the particle assembly site that requires specific Rab proteins and their adaptors is under study. Tetherin is a potent host restriction factor that limits the release of viral particles from the plasma membrane following budding. Vpu is a viral protein that reverses this restriction. The laboratory has defined an important contribution of the tetherin ectodomain to microdomain localization and restriction, and projects are underway to completely define the mechanism by which Vpu disrupts restriction. HIV vaccine-related projects include the design and production of novel virus-like particle immunogens for use in prime-boost immunization regimens, and the study of novel live vectors and new adjuvants for the induction of neutralizing antibodies.