| Autor: |
Neuman BW; The Scripps Research Institute, Department of Neuropharmacology, Division of Virology, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA. bneuman@scripps.edu, Stein DA, Kroeker AD, Paulino AD, Moulton HM, Iversen PL, Buchmeier MJ |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of virology [J Virol] 2004 Jun; Vol. 78 (11), pp. 5891-9. |
| DOI: |
10.1128/JVI.78.11.5891-5899.2004 |
| Abstrakt: |
Conjugation of a peptide related to the human immunodeficiency virus type 1 Tat represents a novel method for delivery of antisense morpholino-oligomers. Conjugated and unconjugated oligomers were tested to determine sequence-specific antiviral efficacy against a member of the Coronaviridae, Mouse hepatitis virus (MHV). Specific antisense activity designed to block translation of the viral replicase polyprotein was first confirmed by reduction of luciferase expression from a target sequence-containing reporter construct in both cell-free and transfected cell culture assays. Peptide-conjugated morpholino-oligomers exhibited low toxicity in DBT astrocytoma cells used for culturing MHV. Oligomer administered at micromolar concentrations was delivered to >80% of cells and inhibited virus titers 10- to 100-fold in a sequence-specific and dose-responsive manner. In addition, targeted viral protein synthesis, plaque diameter, and cytopathic effect were significantly reduced. Inhibition of virus infectivity by peptide-conjugated morpholino was comparable to the antiviral activity of the aminoglycoside hygromycin B used at a concentration fivefold higher than the oligomer. These results suggest that this composition of antisense compound has therapeutic potential for control of coronavirus infection. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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