The heart of the HIV RNA packaging signal?
Alan Rein
Abstract
Mechanisms ensuring faithful reproduction are enforced for viruses, as for all other organisms, by natural selection. As a virus particle is a package containing the viral genome (RNA or DNA, as the case may be) for replication and transmission to the next generation, it is essential that the genome be packaged into the assembling virus particle with high fidelity. In turn, viruses use a wide variety of mechanisms for this selective packaging. HIV type 1 (HIV-1), the causative agent of AIDS, is a retrovirus. The genome within a retrovirus particle is composed of RNA. When it infects a cell, this RNA is copied into double-stranded DNA, which is then integrated into the chromosomal DNA of the cell. How the genomic RNA (viral RNA [vRNA]) is selected for packaging during virus particle assembly is not well understood, and a paper by Ding et al. (1) in PNAS now adds a piece to this intriguing puzzle. Retrovirus particles are roughly spherical, ∼100 to 120 nm in diameter, and are initially assembled primarily from several thousand molecules of the building block, the Gag polyprotein. Thus, it is the Gag polyprotein that selects the vRNA for incorporation into the nascent particle. However, after the virus particle is released from the virus-producing cell, Gag is cleaved by the virus-coded protease into a series of fragments. This “virus maturation” event is a wholesale reorganization of the structure of the virus and is essential for the particle’s ability to undertake an infection of a new host cell. Therefore, while Gag is the principal protein in the immature particle, the predominant proteins in the mature, infectious virus particle are fragments of Gag. There are a number of remarkable aspects to the selective packaging of vRNA during HIV assembly. vRNA is selectively packaged because it contains a “packaging signal” … [↵][1]1Email: reina{at}mail.nih.gov. [1]: #xref-corresp-1-1