The major structural elements of retroviruses are contained in a single polyprotein, Gag, which in HIV-1 comprises the MA, CA, SP1, NC, SP2, and p6 polypeptides. In the immature HIV-1 virion, the domains of Gag are arranged radially with the N-terminal MA domain at the membrane and C-terminal NC-SP2-p6 region nearest the center. This collaborative study from the Jensen and Sundquist labs described the three-dimensional structures of individual immature HIV-1 virions, as obtained by electron cryotomography. The concentric shells of the Gag polyprotein were clearly visible, and radial projections of the different Gag layers revealed patches of hexagonal order within the CA and SP1 shells. Averaging well-ordered unit cells led to a model in which each CA hexamer is stabilized by a bundle of six SP1 helices. This model suggests why the SP1 spacer is essential for assembly of the Gag lattice and how cleavage between SP1 and CA acts as a structural switch controlling maturation.

Structural Models for the Hexameric Lattices Formed by Immature and Mature HIV-1. The N- and C-terminal domains of HIV-1 CA and the SP1 region of Gag are shown in blue, yellow, and magenta, respectively.