How HIV-1 Gag Manipulates Its Host Cell Proteins: A Focus on Interactors of the Nucleocapsid Domain

Abstract

The human immunodeficiency virus (HIV-1) polyprotein Gag (Group-specific antigen) plays a central role in controlling the late phase of the viral lifecycle. Considered to be only a scaffolding protein for a long time, the structural protein Gag plays determinate and specific roles in HIV-1 replication. Indeed, via its different domains, Gag orchestrates the specific encapsidation of the genomic RNA, drives the formation of the viral particle by its auto-assembly (multimerization), binds multiple viral proteins, and interacts with a large number of cellular proteins that are needed for its functions from its translation location to the plasma membrane, where newly formed virions are released. Here, we review the interactions between HIV-1 Gag and 66 cellular proteins. Notably, we describe the techniques used to evidence these interactions, the different domains of Gag involved, and the implications of these interactions in the HIV-1 replication cycle. In the final part, we focus on the interactions involving the highly conserved nucleocapsid (NC) domain of Gag and detail the functions of the NC interactants along the viral lifecycle.

Keywords: Gag; HIV-1; NCp7; Pr55Gag; interactants; nucleocapsid.

Figure 1

Schematic representation of the human immunodeficiency virus (HIV-1) Group-specific antigen (Gag) polyprotein, its different domains and their functions. HIV-1 Gag comprises different domains: matrix (MA), capsid (CA), nucleocapsid (NC), p6 and two spacer peptides (SP1 and SP2). The plasma membrane and phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) located in the inner leaflet are indicated. Gag contains a myristoyl group at its N-terminal end (represented by the blue wave). The nucleocapsid (NC) is a characterized by two highly conserved zinc fingers separated by a basic linker.

Figure 2

Zoom on the interaction of the NC domain of Gag with cellular host factors. The NC domain is highlighted, and its main cellular interacting partners are indicated.