HIV-1 Gag: a Molecular Machine Driving Viral Particle Assembly and Release

HIV-1 and other primate lentiviruses assemble at the plasma membrane and are released by budding from the cell surface. Apart from offering a nonlytic pathway for virus egress, this mode of assembly leads to the acquisition of a host cell-derived lipid envelope that enwraps the nascent viral capsid and protects it from the environment. HIV-1 assembly is controlled primarily by the Gag protein, one of the three gene products that are encoded by all retroviruses. Gag orchestrates assembly by recruiting all the building blocks required for the formation of a fully infectious virion, which in the case of HIV-1 include both viral and cellular components. Furthermore, Gag provides the principal driving force for virus assembly, as illustrated by the fact that HIV-1 Gag can efficiently form virus-like particles even when expressed in the absence of other viral proteins (Gheysen et al., 1989). Gag thus constitutes an autonomous molecular machine for particle assembly.