6/19/2023 0 Comments Fig cookie runInfection with human immunodeficiency virus type 1 (HIV-1) leads to the integration of the provirus into the host genome, resulting in maintained latency in a few CD4 + T cells, which is the main barrier to eradicating HIV-1 from infected individuals by current therapeutics 1, 2. The coevolution of host and retroviral elements involves a fine-tuned interaction to maintain the homeostasis of host genome integrity, development and the immune system in the absence of this homeostasis, diseases or infections can occur. These findings provide new insights into the molecular mechanisms by which proviral latency is initially established and activatable proviruses are resilenced by histone deacetylase recruitment. Conserved suppression effects of TRIM5α orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. ChIP‒qPCR analyses further reveal that the association of TRIM5α with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Mechanistically, TRIM5α binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-κB p50 and Sp1. TRIM5α suppresses TNFα-activated HIV-1 LTR-driven as well as NF-κB- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Knockdown of TRIM5α potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5α. Here, we report an uncharacterized role for TRIM5α in the maintenance of viral latency. Tripartite motif-containing protein 5α (TRIM5α) is generally known to block the postentry events of HIV-1.
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