Herpesvirus alkaline deoxyribonuclease; a possible candidate as a novel target for anti-herpesvirus therapy

Herpesvirus alkaline deoxyribonucrease (DNase) is coded in the genome of all herpesvirus species determined total sequence and is conserved in structure. In order to determine whether the enzyme could be a target for a novel antiherpesvirus therapy, the anti-herpes simplex virus type 1 (HSV-1) activity of antisense oligonucleotide for HSV-1 alkaline DNase was studied. Six antisense phosphorothioate oligonucleotides, targeted to an internal AUG start codon, were designed and evaluated. One of the oligonucleotides, UL12-4, inhibited wild type and thymidine kinase-deficient HSV-1 replication to 21.5 and 19.5% at 40 microM, respectively. The quantity of alkaline DNase mRNA and DNase activity in HSV-1-infected Vero cells was reduced to one eighth and 66.9% of control, respectively, by treatment with 40 microM of UL12-4, but no effect was observed on the quantity of HSV-1 glycoprotein H mRNA (gamma2 gene) or on the replication of Vero cells. These results indicate that UL12-4 inhibits HSV-1 replication by decreasing the amount of alkaline DNase mRNA. The herpesvirus alkaline DNase could be a novel target for anti-herpesvirus drug.