Inhibitory effects of modified oligonucleotides complementary to the leader RNA on the multiplication of mouse hepatitis virus.
Phosphorothioate oligonucleotides (PS-oligo) and PS-oligos with cholesterol conjugates (ChPS-oligo) complementary to the leader RNA of strain JHM of mouse hepatitis virus (JHMV) were more effective inhibitors of viral multiplication than natural oligodeoxynucleotides (PO-oligo) in JHMV-infected DBT cells. PS- and ChPS-oligos were 1,000 times more potent than unmodified PO-oligo. No significant difference was observed in the inhibitory efficiency between PS-oligo and ChPS-oligo. Sequence-dependent inhibition of viral multiplication was shown at low concentrations (0.001-0.1 M) of antisense PS-oligo and ChPS-oligo. Phosphorothioate oligodeoxycytidine, PS-(dC)20, and PS-(dC)20 with cholesterol conjugates, and PS- and ChPS-oligo which have no significant homology to the JHMV sequences, showed inhibitory effects on JHMV multiplication at concentrations higher than 0.5 M. These results showed that PS-oligo and ChPS-oligo were more potent than PO-oligo in the inhibition of JHMV multiplication, and that PS-oligo and ChPS-oligo may inhibit JHMV multiplication by two different mechanisms, that is by sequence-dependent and sequence-independent manners.
Hayashi
M
M
Department of Veterinary Radiology, Rakuno Gakuen University, Ebetsu, Japan.
Maeda
A
A
Kihara
M
M
Arai
S
S
Hanaki
K
K
Nozaki
T
T
D020121:5' Untranslated Regions; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D051379:Mice; D006517:Murine hepatitis virus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D012367:RNA, Viral; D014407:Tumor Cells, Cultured
D020121:5' Untranslated Regions; D000998:Antiviral Agents; D009838:Oligodeoxyribonucleotides; D012367:RNA, Viral