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Despite the success of antiretroviral therapy, human immunodeficiency virus (HIV) cannot be cured because of a reservoir of latently infected cells that evades therapy. To understand the mechanisms of HIV latency, we employed an integrated single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) approach to simultaneously profile the transcriptomic and epigenomic characteristics of ∼ 125,000 latently infected primary CD4+T cells after reactivation using three different latency reversing agents. Differentially expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor (TF) activities across the cell population. We identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%–79% accurate at predicting viral reactivation. Finally, we validated the role of two candidate HIV-regulating factors, FOXP1 and GATA3, in viral transcription. These data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

Understanding dielectric response and charge transport in ion-containing polymers is essential for the design and implementation of these materials in energy-related applications. Our previous study identified the significant impacts of anion chemical composition on ion conduction for poly(ethylene oxide)-based lithium ionomers with polymer-fixed sulfonylimide (MTLi) and sulfonate anions (J. Mater. Chem. C, 2022,10,14569). In this study, we further explore the dielectric response and Li+conduction in the context of different ion states using DFT. The most relevant ion states impacting the dielectric response and Li+conduction are represented with a four-state model. DFT calculation using the cluster-continuum solvation model captures the local solvation effects of poly(ethylene oxide) and reveals low cluster dissociation energy between neutral and charged states. Low cluster dissociation energy explains the weakly aggregated morphology with low aggregation number based on X-ray scattering and implies that Li+rapidly exchanges between different ion states. Consequently, Li+can hop along aggregates for high ion content MTLi, which results in its significant dielectric response, comparable conductivity, and lower Haven ratio despite stronger aggregation than the low ion content counterparts. Different from typical ionomers where raising ion content is detrimental to the ion transport and dielectric response, the understandings based on different ion states for MTLi offer new insights to promote ion conduction and dielectric response for single-ion conducting ionomers.