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Antisense morpholino-oligomers directed against the 5' end of the genome inhibit coronavirus proliferation and growth.
|Title||Antisense morpholino-oligomers directed against the 5' end of the genome inhibit coronavirus proliferation and growth.|
|Publication Type||Journal Article|
|Year of Publication||2004|
|Authors||Neuman BW, Stein DA, Kroeker AD, Paulino AD, Moulton HM, Iversen PL, Buchmeier MJ|
|Journal||Journal of virology|
|Date Published||2004 Jun|
|Keywords||Animals, Base Sequence, Cells, Cultured, Genome, Viral, Mice, Molecular Sequence Data, Morpholines, Morpholinos, Murine hepatitis virus, Oligonucleotides, Antisense, Viral Proteins|
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.
|Alternate Journal||J. Virol.|