Inhibition of human immunodeficiency virus type 1-mediated cytopathic effects by poly(L-lysine)-conjugated synthetic antisense oligodeoxyribonucleotides.
The ability of poly(L-lysine)-conjugated and methylphosphonate-modified synthetic human immunodeficiency virus type 1 (HIV-1) antisense oligodeoxyribonucleotides to protect susceptible host cells from the cytopathic effects of HIV-1 infection was studied. The abundance of viral antigens in oligomer-treated cultures indicated that the oligomers did not significantly affect viral infectivity. Similarly, no significant effects on relative viral RNA accumulation were apparent. The presence of poly(L-lysine)-modified oligomer complementary to the HIV-1 splice donor site resulted in a significant reduction in the production of viral structural proteins and virus titre in infected cultures. In addition, these cells were protected from HIV-1-mediated cytopathic effects while the other cultures rapidly succumbed to the cytotoxic effects of HIV-1 infection. The presence of poly(L-lysine)-conjugated oligomer resulted in the establishment of a persistent HIV-1 infection characterized by a highly productive virus infection in the absence of cell death while treatment of persistently infected cells with phorbol ester resulted in renewed cytopathicity. These results demonstrate the ability of synthetic antisense oligonucleotides to protect susceptible host cells from the cytopathic effects of HIV-1 infection.
Stevenson
M
M
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68105.
Iversen
P L
PL
D015152:Blotting, Northern; D015139:Blotting, Southern; D015704:CD4 Antigens / Q000235:genetics; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects*; D004279:DNA, Viral / Q000032:analysis; D015967:Gene Expression Regulation, Viral; D006678:HIV / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D015345:Oligonucleotide Probes; D011107:Polylysine / Q000008:administration & dosage*; D012045:Regulatory Sequences, Nucleic Acid; D012191:Retroviridae Proteins / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D004279:DNA, Viral; D015345:Oligonucleotide Probes; D012191:Retroviridae Proteins; D011107:Polylysine; D013755:Tetradecanoylphorbol Acetate