Antiviral activity of a chemically stabilized 2‐5A analog upon microinjection into HeLa cells

Abstract
2‐5A[ppp(A2'p) n 5'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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