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

FEBS Letters

Torrence, Paul³  De Clercq, Erik¹  Verhaegen-Lewalle, Martine²  Content, Jean²  Huez, Georges⁴  Imai, Jiro²  Defilippi, Paola² 

[1] Rega Institute for Medical Research, Katholieke Universiteit Leuven,10 Minderbroedersstraat, 3000 Leuven, Belgium;Institut Pasteur du Brabant, Virology Department, Rue Engeland 642,1180 BruxellesBelgium;Laboratory of Chemistry, National Institute of Arthritis, Diabetes, and Digestive and Kidney Disease, National Institutes of Health, Belhesda, MD 20205, USA;Université Libre de Bruxelles, Department of Molecular Biology, 67 Rue des Chevaux, 1640 Rhode St. GeneseBelgium

关键词: Antiviral ativity;    Microinjeclion;    2-5A analog;    Interferon;    dsRNA;    double-stranded RNA;    2-5A;    2 '-5'-oligonucleotides with the general structure ppp(A2' p) n 5 ' A (n = 2 → trimer;    n = 3 → tetramer);    core 2-5A;    5 '-dephosphorylated 2-5A;    thus (A2'p) n 5'A;    RNase L;    2-5A-activated endoribonuclease;    also called ribonuclease F;    EMC virus;    encephalomyocarditis virus;    xylo 2-5A core;    xyloadenosine analogue with the general structure (xyloA2'p)2xyloA;    hexylmorpholine 2-5A analog;    2-5A in which the ribose of the 2'-terminal nucleotide is transformed to an N-hexylmorpholine (azahexapyranose);    specifically;    2-(adenyl)-6-hydroxymethyl-4-hexylmorpholine;   

DOI  :  10.1016/0014-5793(86)80430-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown