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.
Pauls
Eduardo
E
Retrovirology Laboratroy irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Ctra. Del Canyet s/n, Badalona, Barcelona 08916, Spain.
Senserrich
Jordi
J
Clotet
Bonaventura
B
Esté
Jose A
JA
D016923:Cell Death / Q000276:immunology; D002460:Cell Line; D020869:Gene Expression Profiling; D015726:Giant Cells / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D034622:RNA Interference / Q000276:immunology*; D012190:Retroviridae / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects* / Q000276:immunology
D016159:Tumor Suppressor Protein p53