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

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.
AuthorsEduardo Pauls, Jordi Senserrich, Bonaventura Clotet, Jose A Esté
JournalJournal of leukocyte biology (J Leukoc Biol) Vol. 80 Issue 3 Pg. 659-67 (Sep 2006) ISSN: 0741-5400 [Print] United States
PMID16844765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Tumor Suppressor Protein p53
  • 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)

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