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Virology ; 356(1-2): 79-94, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16926043

RESUMO

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.


Assuntos
HIV-1/fisiologia , Macrófagos/virologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/farmacologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Regulação para Cima , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Perfilação da Expressão Gênica , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Interferon-alfa/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Antígenos de Histocompatibilidade Menor , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido
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