Stimulated trans-acting factor of 50 kDa (Staf50) inhibits HIV-1 replication in human monocyte-derived macrophages

• Published in: Virology (New York, N.Y.) N.Y.), 2006-12, Vol.356 (1), p.79-94
• Main Authors: Bouazzaoui, Abdellatif, Kreutz, Marina, Eisert, Veronika, Dinauer, Norbert, Heinzelmann, Anna, Hallenberger, Sabine, Strayle, Jochen, Walker, Russel, Rübsamen-Waigmann, Helga, Andreesen, Reinhard, von Briesen, Hagen
• Format: Article
• Language: English
• Subjects: Cell Line; Cells, Cultured; Gene Expression Profiling; Gene profiling; HIV Infections - virology; HIV replication; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus 1; Humans; Interferon; Interferon-alpha - pharmacology; Lipopolysaccharide; Lipopolysaccharides - pharmacology; Macrophages - immunology; Macrophages - metabolism; Macrophages - virology; Minor Histocompatibility Antigens; Monocytes/Macrophages; Oligonucleotide Array Sequence Analysis; Repressor Proteins - genetics; Repressor Proteins - metabolism; Repressor Proteins - pharmacology; Staf50; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - pharmacology; Tripartite Motif Proteins; Up-Regulation; Virus Replication - drug effects
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.07.025

In order to identify cellular genes which interfere with HIV-1 replication in monocyte-derived macrophages (MAC), cells were stimulated with interferon (IFN) or lipopolysaccharide (LPS) leading to a pronounced inhibition of HIV-1 infection in these cells, and the resulting gene expression was analyzed. Using the microarray technology we identified a gene named Stimulated Trans-Acting Factor of 50  kDa (Staf50), which is known to repress the activity of the HIV-1 LTR. Analysis of the Staf50 expression by real-time PCR showed an overexpression in IFNα (up to 20-fold) and LPS (up to 10-fold)-stimulated MAC as well as in infected cells (up to 3-fold). For stable overexpression, 293 T cells and primary macrophages were transduced with Staf50-IRES-GFP bicistronic pseudotype viruses. After transduction, 293 T CD4/CCR5 and MAC were infected with HIV-1, and virus replication was monitored by p24 ELISA. Overexpression of Staf50 inhibited the HIV-1 infection between 50% and 90% in 293 T CD4/CCR5 as well as in MAC. Our findings suggest that host genetic effects in combination with viral properties determine the susceptibility of an appropriate target cell for HIV-1 infection as well as the replication potential of the virus in the cell resulting in an overall productive infection.