Inhibition of HIV-1 replication by RNA interference of p53 expression.

Abstract

p53 expression and activation have been associated to faster human immunodeficiency virus (HIV) disease progression, most probably by inducing CD4+ T cell death but also through its cooperative effect in the control of viral gene transcription by viral regulatory proteins. Here, we show that RNA interference of p53 in HIV-1 reporter (HeLa P4-R5 MAGI) and lymphoid (SupT1) cell lines blocked HIV-1 and Tat-induced transcription from the HIV-1 promoter and HIV-1 replication in acutely infected cells, suggesting a cooperative role of p53 in HIV-1 transcription. Contrary to SupT1 cells, which encode several mutations on the p53 DNA binding domain, death of HIV-1-induced syncytia was reduced in cocultures of HeLa P4-R5 MAGI with persistently infected HIV-1 cells. To our knowledge, this is the first demonstration of the effect of the loss of function of p53 in HIV-1 replication, which is independent on its classical DNA binding activity. Our results suggest two independent roles for p53 in HIV-1 infection: cooperation in HIV long-terminal repeat transcription and virus-induced cell death.

• Authors: Eduardo Pauls, Jordi Senserrich, Bonaventura Clotet, Jose A Esté
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 80 Issue 3 Pg. 659-67 (Sep 2006) ISSN: 0741-5400 [Print] United States
• PMID: 16844765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Suppressor Protein p53

Topics

• Cell Death (immunology)
• Cell Line
• Gene Expression Profiling
• Giant Cells (immunology, virology)
• HIV-1 (drug effects, immunology, isolation & purification)
• HeLa Cells
• Humans
• RNA Interference (immunology)
• Retroviridae (immunology)
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Sensitivity and Specificity
• Transcription, Genetic (immunology)
• Tumor Suppressor Protein p53 (antagonists & inhibitors, genetics, immunology)
• Virus Replication (drug effects, immunology)