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Inhibition of HIV‐1 replication by RNA interference of p53 expression
Author(s) -
Pauls Eduardo,
Senserrich Jordi,
Clotet Bonaventura,
Esté Jose A.
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0306189
Subject(s) - biology , transcription (linguistics) , hiv long terminal repeat , viral replication , hela , rna interference , syncytium , virology , transcriptional regulation , programmed cell death , virus , transcription factor , microbiology and biotechnology , gene expression , cell culture , rna , gene , long terminal repeat , apoptosis , genetics , philosophy , linguistics
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 encoe 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.