A modular CRISPR screen identifies individual and combination pathways contributing to HIV-1 latency

Transcriptional silencing of latent HIV-1 proviruses entails complex and overlapping mechanisms that pose a major barrier to in vivo elimination of HIV-1. We developed a new latency CRISPR screening strategy, called Latency HIV-CRISPR which uses the packaging of guideRNA-encoding lentiviral vector genomes into the supernatant of budding virions as a direct readout of factors involved in the maintenance of HIV-1 latency. We developed a custom guideRNA library targeting epigenetic regulatory genes and paired the screen with and without a latency reversal agent-AZD5582, an activator of the non-canonical NFκB pathway-to examine a combination of mechanisms controlling HIV-1 latency. A component of the Nucleosome Acetyltransferase of H4 histone acetylation (NuA4 HAT) complex, ING3, acts in concert with AZD5582 to activate proviruses in J-Lat cell lines and in a primary CD4+ T cell model of HIV-1 latency. We found that the knockout of ING3 reduces acetylation of the H4 histone tail and BRD4 occupancy on the HIV-1 LTR. However, the combination of ING3 knockout accompanied with the activation of the non-canonical NFκB pathway via AZD5582 resulted in a dramatic increase in initiation and elongation of RNA Polymerase II on the HIV-1 provirus in a manner that is nearly unique among all cellular promoters

Searching beyond Gd for magnetocaloric frameworks: magnetic properties and interactions of the Ln(HCO2)3 series

This study probes the magnetic properties and interactions of the Ln(HCO2)3 (Ln = Tb3+–Er3+) frameworks. We show that the magnetocaloric effect of Tb(HCO2)3 is significantly higher above 4 K in moderate magnetic fields compared to the promising Gd(HCO2)3. While the peak performance of Tb(HCO2)3 is lower than Gd(HCO2)3, we also find that the Gd-rich members of the solid solution Gd1−xTbx(HCO2)3 blend the advantages of both end-members. Using neutron diffraction experiments, Tb(HCO2)3 is found to be antiferromagnetic below 1.7 K with ferromagnetic face-sharing chains and antiferromagnetic coupling between them. Analysis of magnetic diffuse scattering of the paramagnetic phase indicates that ferromagnetic coupling is retained, and it is likely that this plays a role in improving its magnetocaloric performance in low fields