Summary

Interactions between and trafficking of the Gag and Gag-Pro-Pol precursors are central to the assembly of the retroviral particle. These interactions are now being studied at the molecular level using a variety of powerful tools ranging from the replication of mutant viruses in cell culture to the assembly of viral capsids in vitro. The important steps of membrane association, Gag oligomerization, RNA recognition and packaging, particle budding, Env incorporation, Pro-Pol dimerization, and protease-mediated processing are areas of continued interest. Defining the molecular details of specificity and control for each of these steps will represent major advances.

Other features of assembly remain more mysterious. The fundamental difference between assembly at the membrane (for the type-C viruses) versus assembly in the cytoplasm (for the type-B and -D viruses) is unexplained. The absence of accessory proteins in many retroviruses suggests that the assembly and maturation process is largely self-driven by Gag and Gag-Pro-Pol. Yet the involvement of novel accessory proteins in the formation of infectious virions in the primate lentiviruses points to another layer of complexity that is only now being perceived. In an analogous way, the potential role of host proteins is only beginning to be appreciated.

Structural information is becoming available for all of the mature protein products of Gag, Pro, and Pol, and information about their structures in the context of the precursors can be anticipated. These structures will bring a face to the many interactions that are being uncovered through a variety of molecular, biochemical, and biophysical approaches. Collectively, these approaches will provide a view of assembly and maturation that is sufficiently clear both to be intellectually satisfying and to provide targets for designed intervention.