https://www.selleckchem.com/products/rottlerin.html Clinical trials investigating HDACi to reverse HIV-1 latency aim to expose reservoirs in antiretroviral-treated individuals to clearance by immune effectors, yet have not driven measurable reductions in the frequencies of infected cells. We therefore investigated the effects of the class-I-selective HDACi nanatinostat and romidepsin on various blocks to latency reversal and elimination, including viral splicing, antigen presentation, and CD8+ T cell function. In ex vivo CD4+ T cells from ARV-suppressed individuals, both HDACi significantly induced viral transcription but not splicing, nor supernatant HIV-1 RNA. In an HIV-1 latency model using autologous CD8+ T cell clones as biosensors of antigen presentation, neither HDACi-treated CD4+ T cell condition induced clone degranulation. Both HDACi also impaired the function of primary CD8+ T cells in viral inhibition assays, with less impairment using nanatinostat. These findings suggest spliced or cell-free HIV-1 RNA are more indicative of antigen expression thansights into the limited activity of HDACi in clinical trials, and offers direction for future approaches. Copyright © 2020 American Society for Microbiology.The innate immune system is normally programmed for immediate but transient upregulation in response to invading pathogens and interferon (IFN)-stimulated gene (ISG) activation is a central feature. In contrast, chronic innate immune system activation is typically associated with autoimmunity and a broad array of autoinflammatory diseases that include the interferonopathies. Here, we studied retroviral susceptibility in a transgenic mouse model with life-long innate immune system hyper-activation. The mice transgenically express low levels of a picornaviral RNA-dependent RNA polymerase (RdRP), which synthesizes double-stranded RNAs that are sensed by MDA5 to trigger constitutive upregulation of many ISGs. However, in striking counterpoint to the paradigm es