Coordination of Genomic RNA Packaging with Viral Assembly in HIV-1

Abstract

The tremendous progress made in unraveling the complexities of human immunodeficiency virus (HIV) replication has resulted in a library of drugs to target key aspects of the replication cycle of the virus. Yet, despite this accumulated wealth of knowledge, we still have much to learn about certain viral processes. One of these is virus assembly, where the viral genome and proteins come together to form infectious progeny. Here we review this topic from the perspective of how the route to production of an infectious virion is orchestrated by the viral genome, and we compare and contrast aspects of the assembly mechanisms employed by HIV-1 with those of other RNA viruses.

Keywords: HIV-1; RNA; assembly; packaging.

Figure 1

Overview of the assembly pathway of human immunodeficiency virus type 1 (HIV-1). The viral protein Rev facilitates efficient export of unspliced genomic RNA (gRNA) from the nucleus. Upon entering the cytoplasm, the gRNA can adopt two conformations, which permit either translation or dimerization to form a structure which is selectively packaged by group-specific antigen (Gag). Gag trafficking to the plasma membrane is linked to the mechanism of nuclear export of gRNA, and requires RNA binding to the matrix domain to inhibit binding to intracellular membranes. Multimerized Gag recruits the host endosomal sorting complexes required for transport (ESCRT) machinery for budding, including ALIX, which binds both the p6 and nucleocapsid (NC) domains. Following release immature virions undergo proteolytic maturation (cleavage sites in Gag indicated by arrows) leading to production of infectious virus particles.