Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly

HIV-1 undergoes a two-step assembly process. First, an immature noninfectious particle is assembled, which leaves the infected cell. Second, the structural protein, Gag, is cleaved in the virus by the viral protease, and this leads to formation of the infectious virus. The immature virus particle therefore represents the key intermediate in HIV-1 assembly. There is currently no high-resolution information available on the arrangement of Gag within immature HIV-1. We have assembled part of HIV-1 Gag in vitro to form immature virus-like tubular protein arrays, and have solved a subnanometer-resolution structure of these arrays by using cryo-EM and tomography. This structure reveals interactions of the C-terminal capsid domain of Gag that are critical for HIV-1 assembly.