TY - JOUR
T1 - Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication
AU - Pesce, Caterina D.
AU - Bolacchi, Francesca
AU - Bongiovanni, Barbara
AU - Cisotta, Federica
AU - Capozzi, Marcella
AU - Diviacco, Silvia
AU - Quadrifoglio, Franco
AU - Mango, Ruggiero
AU - Novelli, Giuseppe
AU - Mossa, Giuseppe
AU - Esposito, Claudio
AU - Ombres, Domenico
AU - Rocchi, Giovanni
AU - Bergamini, Alberto
PY - 2005/4
Y1 - 2005/4
N2 - Highly active antiretroviral therapy (HAART) is unlikely to affect reservoirs of HIV in latently infected cells. Anti-gene compounds, such as peptide nucleic acids (PNAs), which block transcriptional activity via sequence-specific invasion of double-stranded DNA may be an effective strategy to target cells harbouring proviral HIV DNA. Here we show that a PNA oligomer (PNAHIV), 15 bases in length, linked to a nuclear localization signal (NLS), substantially suppressed HIV-1 replication in chronically infected lymphocytes and macrophages and efficiently prevented mitogen-induced HIV-1 reactivation in lymphocytes, as determined by HIV-p24 antigen production in supernatants and FACS analysis for intracellular HIV accumulation. In contrast, a mismatched PNA did not show any effect on HIV expression. Semi-quantitative RT-PCR and quantitative real-time RT-PCR demonstrated a decrease of HIV RNA expression in infected cells treated by PNAHIV indicating that inhibition of HIV-1 replication occurred at the transcription step. In conclusion, the use of anti-gene PNA to target the HIV-1 proviral DNA in the quest for new antiretroviral agents appears quite promising.
AB - Highly active antiretroviral therapy (HAART) is unlikely to affect reservoirs of HIV in latently infected cells. Anti-gene compounds, such as peptide nucleic acids (PNAs), which block transcriptional activity via sequence-specific invasion of double-stranded DNA may be an effective strategy to target cells harbouring proviral HIV DNA. Here we show that a PNA oligomer (PNAHIV), 15 bases in length, linked to a nuclear localization signal (NLS), substantially suppressed HIV-1 replication in chronically infected lymphocytes and macrophages and efficiently prevented mitogen-induced HIV-1 reactivation in lymphocytes, as determined by HIV-p24 antigen production in supernatants and FACS analysis for intracellular HIV accumulation. In contrast, a mismatched PNA did not show any effect on HIV expression. Semi-quantitative RT-PCR and quantitative real-time RT-PCR demonstrated a decrease of HIV RNA expression in infected cells treated by PNAHIV indicating that inhibition of HIV-1 replication occurred at the transcription step. In conclusion, the use of anti-gene PNA to target the HIV-1 proviral DNA in the quest for new antiretroviral agents appears quite promising.
KW - HIV
KW - Latent infection
KW - Peptide nucleic acid (PNA)
KW - Proviral DNA
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U2 - 10.1016/j.antiviral.2004.12.001
DO - 10.1016/j.antiviral.2004.12.001
M3 - Article
C2 - 15781127
AN - SCOPUS:20144365614
VL - 66
SP - 13
EP - 22
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 1
ER -