In this article, Eric Freed reviews recent progress in elucidating the steps involved in HIV-1 assembly, release and maturation, highlighting how these events are orchestrated by the viral Gag precursor protein and how this information is being used to develop novel anti-HIV-1 therapeutics. Major advances have occurred in recent years in our understanding of HIV-1 assembly, release and maturation, as work in this field has been propelled forwards by developments in imaging technology, structural biology, and cell and molecular biology. This increase in basic knowledge is being applied to the development of novel inhibitors designed to target various aspects of virus assembly and maturation. This Review highlights recent progress in elucidating the late stages of the HIV-1 replication cycle and the related interplay between virology, cell and molecular biology, and drug discovery.

HIV-1 assembly, release and maturation

Global changes in the RNA binding specificity of HIV-1 gag regulate virion genesis.

The 5' leader of the HIV-1 genome contains conserved elements that direct selective packaging of the unspliced, dimeric viral RNA into assembling particles. By using a (2)H-edited nuclear magnetic resonance (NMR) approach, we determined the structure of a 155-nucleotide region of the leader that is independently capable of directing packaging (core encapsidation signal; Ψ(CES)). The RNA adopts an unexpected tandem three-way junction structure, in which residues of the major splice donor and translation initiation sites are sequestered by long-range base pairing and guanosines essential for both packaging and high-affinity binding to the cognate Gag protein are exposed in helical junctions. The structure reveals how translation is attenuated, Gag binding promoted, and unspliced dimeric genomes selected, by the RNA conformer that directs packaging.

/pdf/structure-of-the-hiv-1-rna-packaging-signal-41c2kx8w9z.pdf

Structure of the HIV-1 RNA packaging signal

In this review article, the fundamentals of electrochemical reactions involving metal hydrides are explained, followed by a report of recent progress in hydrogen storage alloys for electrochemical applications. The status of various alloy systems, including AB₅, AB₂, A₂B₇-type, Ti-Ni-based, Mg-Ni-based, BCC, and Zr-Ni-based metal hydride alloys, for their most important electrochemical application, the nickel metal hydride battery, is summarized. Other electrochemical applications, such as Ni-hydrogen, fuel cell, Li-ion battery, air-metal hydride, and hybrid battery systems, also have been mentioned.

/pdf/the-current-status-of-hydrogen-storage-alloy-development-for-250ciqt8ke.pdf

The Current Status of Hydrogen Storage Alloy Development for Electrochemical Applications

Coronavirus genomic RNA packaging.

The 5'-leader of the HIV-1 genome regulates multiple functions during viral replication via mechanisms that have yet to be established. We developed a nuclear magnetic resonance approach that enabled direct detection of structural elements within the intact leader (712-nucleotide dimer) that are critical for genome packaging. Residues spanning the gag start codon (AUG) form a hairpin in the monomeric leader and base pair with residues of the unique-5' region (U5) in the dimer. U5:AUG formation promotes dimerization by displacing and exposing a dimer-promoting hairpin and enhances binding by the nucleocapsid (NC) protein, which is the cognate domain of the viral Gag polyprotein that directs packaging. Our findings support a packaging mechanism in which translation, dimerization, NC binding, and packaging are regulated by a common RNA structural switch.

https://science.sciencemag.org/content/sci/334/6053/242.full.pdf

Azra Hosic

Papers

NMR Detection of Structures in the HIV-1 5'-Leader RNA that Regulate Genome Packaging

Structure of the HIV-1 RNA packaging signal