SUMMARY BET proteins commonly activate cellular gene expression, yet inhibiting their recruitment paradoxically reactivates latent HIV-1 transcription. Here we identify the short isoform of BET family member BRD4 (BRD4S) as a corepressor of HIV-1 transcription. We found that BRD4S was enriched in chromatin fractions of latently infected T cells and was more rapidly displaced from chromatin upon BET inhibition than the long isoform. BET inhibition induced marked nucleosome remodeling at the latent HIV-1 promoter, which was dependent on the activity of BAF, a SWI/SNF chromatin-remodeling complex with known repressive functions in HIV-1 transcription. BRD4S directly bound BRG1, a catalytic subunit of BAF, via its bromo- and ET domains and was necessary for BRG1 recruitment to latent HIV-1 chromatin. Using ChIP-seq combined with ATAC-seq data, we found that the latent HIV-1 promoter phenotypically resembles endogenous LTR sequences, pointing to a select role of BRD4S:BRG1 complexes in genomic silencing of invasive retroelements.

CRS can be divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps. Some individuals with CRSwNP do not respond to standard-of-care medical and surgical management. For these individuals, targeted biologic agents are emerging as an important therapeutic alternative. In this review, we described the most-relevant studies that addressed the use of anti-immunoglobulin E (omalizumab), anti-interleukin 5 (mepolizumab and reslizumab), and anti-interleukin 4/interleukin 13 (dupilumab) monoclonal antibodies for the treatment of CRSwNP. In addition, we discussed the importance of some of these clinical trials in identifying new CRS endotypes based on distinct inflammatory profiles.

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