TY  - JOUR
JF  - Retrovirology
ID  - heidok20004
AV  - public
TI  - HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter
SP  - 1
EP  - 8
PB  - BioMed Central
VL  - 12
IS  - 104
Y1  - 2015///
SN  - 1742-4690
CY  - London
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/20004/
N2  - Background: Intracellular defense proteins, also referred to as restriction factors, are capable of interfering with different steps of the viral life cycle. Among these, we have shown that Tripartite motif 22 (TRIM22) suppresses basal as well as phorbol ester-induced HIV-1 long terminal repeat (LTR)-mediated transcription, independently of its E3 ubiquitin ligase activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) binding to the U3 region and Tat interaction with the TAR region of the HIV-1 LTR. As basal HIV-1 transcription is driven by the transcription factor specificity protein 1 (Sp1), we have investigated whether TRIM22 could interfere with Sp1-driven transcriptional activation of the HIV-1 LTR.   Findings: 293T cells, devoid of endogenous TRIM22 expression, were transfected with a TRIM22-expressing plasmid together with reporter plasmids driven by the HIV-1 LTR promoter either containing or lacking Sp1 binding sites or with reporter plasmids driven by non-viral promoter sequences either containing or lacking the three Sp1 binding sites from the HIV-1 LTR. These reporter assays showed that TRIM22 efficiently inhibited Sp1-driven transcription. Knocking down TRIM22 expression in the CD4+ SupT1 T cell line increased the replication of Sp1-dependent HIV-1 variants. TRIM22 did not interact with Sp1, but prevented binding of Sp1 to the HIV-1 promoter, as demonstrated in protein-DNA pull down and chromatin immunoprecipitation assays.   Conclusion: TRIM22 acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter.
A1  - Turrini, Filippo
A1  - Marelli, Sara
A1  - Kajaste-Rudnitski, Anna
A1  - Lusic, Marina
A1  - Van Lint, Carine
A1  - Das, Atze T.
A1  - Harwig, Alex
A1  - Berkhout, Ben
A1  - Vicenzi, Elisa
ER  -