Antiviral activity of a chemically stabilized 2-5A analog upon microinjection into HeLa cells.
2-5A[ppp(A2'p)n5'A] has been implicated as a mediator in the antiviral action of interferon. Its direct evaluation as an indicator of virus replication is hampered by two limitations: its inability to penetrate intact cells, and its rapid intracellular degradation by (2'-5')phosphodiesterase. These problems could be overcome by using a microinjection technique whereby a phosphodiesterase-resistant analog of 2-A, in which the 2'-terminals adenosine residue is replaced by 2-(9-adenyl)-6-hydroxy-methyl-4-hexylmorpholine, was injected into individual HeLa cells before infection with mengovirus or vesicular stomatitis virus (VSV). This comparative assay with two representatives of different virus classes in a single experimental system pointed to the high sensitivity of VSV to inhibition by 2-5A oligonucleotides, in contrast with the low sensitivity of mengovirus. Microinjection of the hexylmorpholine 2-5A analog led to a much greater reduction in mengovirus yield than did microinjection of 2-5A itself.
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P
Defilippi
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Huez
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M
Verhaegen-Lawalle
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E
De Clercq
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Imai
P
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Torrence
J
J
Content
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D008574:Mengovirus / Q000187:drug effects; D008845:Microinjections; D009843:Oligoribonucleotides / Q000494:pharmacology*; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000227:Adenine Nucleotides; D000998:Antiviral Agents; D009843:Oligoribonucleotides; C023505:2',5'-oligoadenylate; D007372:Interferons