Stimulated trans-acting factor of 50 kDa (Staf50) inhibits HIV-1 replication in human monocyte-derived macrophages.
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 IFNalpha (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.
Bouazzaoui
Abdellatif
A
Georg-Speyer-Haus, Institute for Biomedical Research, 60596 Frankfurt/M., Germany.
Kreutz
Marina
M
Eisert
Veronika
V
Dinauer
Norbert
N
Heinzelmann
Anna
A
Hallenberger
Sabine
S
Strayle
Jochen
J
Walker
Russel
R
Rübsamen-Waigmann
Helga
H
Andreesen
Reinhard
R
von Briesen
Hagen
H
D002460:Cell Line; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D015778:Minor Histocompatibility Antigens; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D000070584:Tripartite Motif Proteins; D015854:Up-Regulation; D014779:Virus Replication / Q000187:drug effects*
D016898:Interferon-alpha; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; C094314:TRIM22 protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins