Anti-gene peptide nucleic acid targeted to proviral HIV-1 DNA inhibits in vitro HIV-1 replication.
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
Caterina D
CD
Department of Experimental Medicine and Biochemical Sciences, University of Roma Tor Vergata, Rome, Italy.
Bolacchi
Francesca
F
Bongiovanni
Barbara
B
Cisotta
Federica
F
Capozzi
Marcella
M
Diviacco
Silvia
S
Quadrifoglio
Franco
F
Mango
Ruggiero
R
Novelli
Giuseppe
G
Mossa
Giuseppe
G
Esposito
Claudio
C
Ombres
Domenico
D
Rocchi
Giovanni
G
Bergamini
Alberto
A
D002478:Cells, Cultured; D004279:DNA, Viral / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D008214:Lymphocytes / Q000821:virology; D009000:Monocytes / Q000821:virology; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D011533:Proviruses / Q000187:drug effects / Q000235:genetics; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D020135:Peptide Nucleic Acids