TRIM5α recruits HDAC1 to p50 and Sp1 and promotes H3K9 deacetylation at the HIV-1 LTR

Tripartite motif-containing protein 5 alpha (TRIM5 alpha) is generally known to block the postentry events of HIV-1. Here, we report an uncharacterized role for TRIM5 alpha in the maintenance of viral latency. Knockdown of TRIM5 alpha potentiates the transcription of HIV-1 in multiple latency models, which is reversed by shRNA-resistant TRIM5 alpha. TRIM5 alpha suppresses TNF alpha-activated HIV-1 LTR-driven as well as NF-kappa B- and Sp1-driven gene expression, with the RING and B-box 2 domains being the essential determinants. Mechanistically, TRIM5 alpha binds to and enhances the recruitment of histone deacetylase 1 (HDAC1) to NF-kappa B p50 and Sp1. ChIPqPCR analyses further reveal that the association of TRIM5 alpha with HIV-1 LTR induces HDAC1 recruitment and local H3K9 deacetylation. Conserved suppression effects of TRIM5 alpha orthologs from multiple species on both HIV-1 and endo-retroelement HERV-K LTR activities have also been demonstrated. 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.