BAG-3 protein suppresses HIV-1 promoter activity by binding NF-kB p65 in microglia and astrocytic cells

• Published in: Journal of neurovirology 2006-05, Vol.12, p.71-71
• Main Authors: Rosati, A, Leone, A, Khalili, K, Turco, M C
• Format: Article
• Language: English
• Subjects: Human immunodeficiency virus 1
• ISSN: 1355-0284

Co-chaperone proteins that share the Bcl-2-associated athanogene (BAG) domain are involved in a number of cellular processes, including proliferation and apoptosis. Among BAG family members there is BAG3, also known as CAIR-1 or Bis, that binds to Hsp70, phospholipase C-gamma (PLC-gamma) and possibly other partners. High levels of BAG3 protein have been found in several disease models. We observed increased expression of BAG3 protein in the cytoplasm of reactive astrocytes in the cortex of a case of HIV encephalopathy by immunohistochemstry. To investigate the effect of increased levels of BAG3 protein on HIV-1 replication, we performed functional assays using a HIV-1 LTR (-120, +66) driven firefly luciferase vector. In particular, we analyzed the effect of overexpressed BAG3 on the ability of NF-( Kappa )B p65 and Tat to activate HIV-1 LTR promoter, in human astrocytic cells, U87MG and in human primary colture of microglia. We found that increased levels of BAG3 protein inhibit the binding of NF-( Kappa )B p65 to the ( Kappa )B-binding motifs of the viral promoter, as assessed by EMSA and ChIP assays. Further analysis demonstrated that this effect is mediated by the direct binding of NF-( Kappa )B p65 to the full length BAG3 protein. Our results suggest a new mechanism to control HIV-1 replication in infected astroglial cells.