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TRIM22 Inhibits HIV-1 Transcription Independently of Its E3 Ubiquitin Ligase Activity, Tat, and NF-κB-Responsive Long Terminal Repeat Elements.
- Source :
-
Journal of Virology . May2011, Vol. 85 Issue 10, p5183-8196. 14p. - Publication Year :
- 2011
-
Abstract
- Previous studies identified clones of the U937 promonocytic cell line that were either permissive or nonpermissive for human immunodeficiency virus type 1 (HIV-1) replication. These clones were investigated further in the search for host restriction factors that could explain their differential capacity to support HIV-1 replication. Among known HIV-1 restriction factors screened, tripartite motif-containing protein 22 (TRIM22) was the only factor constitutively expressed in nonpermissive and absent in permissive U937 cells. Stable TRIM22 knockdown (KD) rescued HIV-1 long-terminal-repeat (LTR)-driven transcription in KD-nonpermissive cells to the levels observed in permissive cells. Conversely, transduction-mediated expression of TRIM22 in permissive cells reduced LTR-driven luciferase expression by ∼7-fold, supporting a negative role of TRIM22 in HIV-1 transcription. This finding was further confirmed in the human T cell line A3.01 expressing TRIM22. Moreover, overexpression of TRIM22 in 293T cells significantly impaired basal and phorbol myristate acetate-ionomycin-induced HIV-1 LTR-driven gene expression, whereas inhibition of tumor necrosis factor alpha-induced viral transcription was a consequence of lower basal expression. In agreement, TRIM22 equally inhibited an LTR construct lacking the tandem NF-κB binding sites. In addition, TRIM22 did not affect Tat-mediated LTR transactivation. Finally, these effects were independent of TRIM22 E3 ubiquitin-ligase activity. In the context of replication-competent virus, significantly higher levels of HIV-1 production were observed in KD-nonpermissive versus control nonpermissive U937 cells after infection. In contrast, lower peak levels of HIV-1 replication characterized U937 and A3.01 cells expressing TRIM22 versus their control transduced counterpart. Thus, nuclear TRIM22 significantly impairs HIV-1 replication, likely by interfering with Tat- and NF-κB-independent LTR-driven transcription. [ABSTRACT FROM AUTHOR]
- Subjects :
- *UBIQUITIN
*HIV
*VIRAL replication
*CELL lines
*LUCIFERASES
*GENE expression
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 85
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 60667192
- Full Text :
- https://doi.org/10.1128/JVI.02302-10