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 (PNA(HIV)), 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 PNA(HIV) 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.

Pesce, C.d., Bolacchi, F., Bongiovanni, B., Cisotta, F., Capozzi, M., Diviacco, S., et al. (2005). Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication. ANTIVIRAL RESEARCH, 66(1), 13-22 [10.1016/j.antiviral.2004.12.001].

Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication

PESCE, CATERINA DELFINA;CAPOZZI, MARCELLA;NOVELLI, GIUSEPPE;ESPOSITO, CARLA;ROCCHI, GIOVANNI;BERGAMINI, ALBERTO
2005-04-01

Abstract

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 (PNA(HIV)), 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 PNA(HIV) 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.
apr-2005
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/03 - GENETICA MEDICA
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
virus replication; DNA, viral; virus latency; cells, cultured; peptide nucleic acids; monocytes; lymphocytes; HIV-1; proviruses
Pesce, C.d., Bolacchi, F., Bongiovanni, B., Cisotta, F., Capozzi, M., Diviacco, S., et al. (2005). Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication. ANTIVIRAL RESEARCH, 66(1), 13-22 [10.1016/j.antiviral.2004.12.001].
Pesce, Cd; Bolacchi, F; Bongiovanni, B; Cisotta, F; Capozzi, M; Diviacco, S; Quadrifoglio, F; Mango, R; Novelli, G; Mossa, G; Esposito, C; Ombres, D; Rocchi, G; Bergamini, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/29386
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