Role of host factors in subcellular trafficking of Gag proteins and genomic RNA leading to virion assembly

The retroviral Gag protein orchestrates the assembly of virions and has been called the “virus particle–making machine” (Dickson et al., 1984). Gag proteins undergo a complex journey through the cell, with populations observed in the nucleus and cytoplasm, and they ultimately arrive at the plasma membrane where new virions are released through the process of budding. As Gag proteins travel throughout the cell, they oligomerize and bind to viral components, including the Gag-Pol and Env proteins and the genomic RNA, recruiting them into virions. During its travels, Gag also associates with a wide range of host factors, including RNAs, proteins, and lipids. In this chapter, we discuss the cellular interactomes of Gag proteins of different retroviruses; some interacting factors are transient partners that play a role in particle assembly, whereas others remain associated with Gag and are packaged into virus particles. In many cases, the potential functions of these Gag-interacting factors remain unexplored, supporting the need for further studies that could lead to novel inhibitors of virus assembly.