eprintid: 20004
rev_number: 11
eprint_status: archive
userid: 1589
dir: disk0/00/02/00/04
datestamp: 2016-02-15 13:45:58
lastmod: 2016-05-09 11:35:54
status_changed: 2016-02-15 13:45:58
type: article
metadata_visibility: show
creators_name: Turrini, Filippo
creators_name: Marelli, Sara
creators_name: Kajaste-Rudnitski, Anna
creators_name: Lusic, Marina
creators_name: Van Lint, Carine
creators_name: Das, Atze T.
creators_name: Harwig, Alex
creators_name: Berkhout, Ben
creators_name: Vicenzi, Elisa
title: HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter
subjects: 570
subjects: 610
divisions: 911700
abstract: 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.
date: 2015
publisher: BioMed Central
id_scheme: DOI
id_number: http://dx.doi.org/10.1186/s12977-015-0230-0
ppn_swb: 1656556707
own_urn: urn:nbn:de:bsz:16-heidok-200042
language: eng
bibsort: TURRINIFILHIV1TRANSC2015
full_text_status: public
publication: Retrovirology
volume: 12
number: 104
place_of_pub: London
pagerange: 1-8
issn: 1742-4690
citation:   Turrini, Filippo ; Marelli, Sara ; Kajaste-Rudnitski, Anna ; Lusic, Marina ; Van Lint, Carine ; Das, Atze T. ; Harwig, Alex ; Berkhout, Ben ; Vicenzi, Elisa  (2015) HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter.  Retrovirology, 12 (104).  pp. 1-8.  ISSN 1742-4690     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/20004/1/12977_2015_Article_230.pdf