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127 Characterization of Tripartite-Motif (TRIM) 22-Mediated Inhibition of HIV-1 Transcription

Kajaste-Rudnitski, A1; Marell, S1; Pertel, T3; Poli, G2; Luban, J3; Vicenzi, E1

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 51
doi: 10.1097/01.qai.0000397315.09589.b3

1Viral Pathogens and Biosafety Unit; 2AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milano, Italy; 3Department of Microbiology and Molecular Medicine University of Geneva, 1 Rue Michel Servet, CH-1211 Geneva, Switzerland

The family of TRIM proteins, including TRIM5α, has been previously described as capable of interfering with HIV-1 or SIV at different steps of the retroviral life cycle. In a model of permissive (P) and non-permissive (NP) clones of the promonocytic U937 cell line, we have recently observed that endogenous TRIM22 is responsible for impairing HIV-1 long terminal repeat (LTR)-driven gene expression in NP cells, whereas its expression is absent in P cells (AKR et al., submitted). HIV transcription is regulated by a variety of cis-acting DNA sequence elements within the proviral LTR, responsive to specific host transcription factors. With the aim of identifying which of these factors could be involved in the TRIM22-mediated inhibition of HIV-1 transcription, an HIV-1 LTR Luciferase (Luc) reporter construct was transfected in 293T cells along with increasing amounts of TRIM22-expressing plasmid followed by cell stimulation with phorbol myristate acetate (PMA) plus ionomycin (I). TRIM22 expression inhibited both basal and PMA+I induced HIV-1 LTR activity whereas Tat-mediated transactivation of HIV-1 LTR was not affected. Furthermore, increasing amounts of TRIM22-expressing plasmid inhibited NFAT-1, NF-kB or AP-1-driven Luc expression to basal level in 293T cells along with, followed by stimulation with PMA+I. These results highlight a broad inhibitory effect of TRIM22 on Tat-independent HIV-1 LTR driven transcription. Since no DNA interacting domains are known to be present in TRIM22 our results suggest that this host factor might either interact, directly or indirectly, with the above mentioned cellular transcription factors or that it may act via an epigenetic mechanism regulating HIV-1 transcription.

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