Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9000951 | Antiviral Research | 2005 | 10 Pages |
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 (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.
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Authors
Caterina D. Pesce, Francesca Bolacchi, Barbara Bongiovanni, Federica Cisotta, Marcella Capozzi, Silvia Diviacco, Franco Quadrifoglio, Ruggiero Mango, Giuseppe Novelli, Giuseppe Mossa, Claudio Esposito, Domenico Ombres, Giovanni Rocchi, Alberto Bergamini,