J Korean Soc Microbiol.
1999 Jun;34(3):233-243.
Antiviral Effect of Antisense Phosphorothioate Oligonucleotides Targeted to Herpes Simplex Virus
Abstract
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To search the effective antisense oligonucleotide that inhibit the growth of Herpes simplex virus type 1 (HSV-1), six kinds of phosphorothioate oligodeoxynucleotides (S-ODNs) were synthesized and the antiviral activity was assessed by measuring cytopathic effect in Vero cells infected with HSV-1. Of the three dodecamer S-ODNs, cornplernentary to the translation initiation site of IE2 (AS2) and scrambled S-ODN (AS1) showed more significant antiherpetic activity than AS4 complementary to the IE4. Accordingly, the antiviral effect of dodecamer S-ODN was not specific. In contrast to the no inhibitory effect of sense strand S-ODN of ICP8 (AS6), two S-ODNs complementary to the translation initiation site of ICP8 (AS3) and that of IE1 (AS5) showed potent antiherpetic activity assessed in vitro HSV-1 virus yield assay. Antiherpetic effect of AS3 was decreased in proportion to the addition of AS6. The synthesis of viral protein ICPS and IE1 were inhibited in AS3 and AS5 treated HSV-1 infected Vero cells, respectively. These findings suggest that antiherpetic effect of AS3 is specifically mediated by targeting ICPS. S-ODNs had no effect on Vero cell viability. The data suggest that the 19-mer S-ODNs may be effective in antiviral chemotherapy.