CryoEM Structures and Atomic Model of the HIV-1 Strand Transfer Complex Intasome

HIV-1, like all retroviruses, irreversibly inserts a viral DNA (vDNA) copy of its RNA genome into host target DNA (tDNA). The intasome, a higher-order nucleoprotein complex composed of viral integrase (IN) and the ends of linear vDNA, mediates integration. Productive integration into host chromatin results in the formation of the Strand Transfer Complex (STC) containing catalytically joined vDNA and tDNA. HIV-1 intasomes have been refractory to high-resolution structural studies. Here, using a soluble IN fusion protein, we present a high-resolution cryo-electron microscopy (cryoEM) structure of the core tetrameric HIV-1 STC and a higher-order form that adopts distinct domain rearrangements. The unique manner of STC assembly highlights how HIV-1 can use the common retroviral intasome core architecture to accommodate different IN domain modules for integration.