BRD proteins in human retroviral infection: emerging evidence from HIV-1 and future perspectives for HTLV-1

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Human retroviruses, including Human Immunodeficiency Virus Type 1 (HIV-1) and Human T-cell Leukemia Virus Type 1 (HTLV-1), remain major global health challenges because of their ability to establish persistent infections and evade host immune responses. Viral persistence depends on the exploitation of host epigenetic and transcriptional machinery, particularly chromatin-remodeling complexes and bromodomain-containing proteins. Bromodomain-containing protein 9 (BRD9), an epigenetic reader and core component of the non-canonical BRG1 (Brahma-related gene 1)/BRM-associated factor (ncBAF) complex, regulates chromatin accessibility, enhancer activity, transcription, and immune signaling. While the roles of BRD4 and other bromodomain and extra-terminal (BET) proteins in retroviral infection are well established, the contribution of BRD9 has only recently emerged. In HIV-1 infection, bromodomain proteins regulate viral transcription, latency, and reactivation by modulating chromatin organization and transcriptional elongation. Recent studies identify BRD9 as a novel regulator of HIV-1 latency through ncBAF-dependent control of proviral transcription, highlighting its potential as a therapeutic target. In contrast, direct evidence linking BRD9 to HTLV-1 infection is currently unavailable. However, the established roles of BRD4 and other BET proteins in HTLV-1 transcription, oncogenic signaling, and Adult T-cell Leukemia/Lymphoma (ATLL) progression suggest that other BRDs proteins may also participate in similar regulatory pathways. This review synthesizes current evidence on the emerging role of BRDs proteins in retroviral biology, highlights critical knowledge gaps, and proposes future mechanistic and translational research directions to clarify its therapeutic potential in HIV-1 and HTLV-1 infection.