title: Herpesvirus alkaline deoxyribonuclease; a possible candidate as a novel target for anti-herpesvirus therapy.
abstract: 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.
authors.affiliation: Department of Microbiology, Asahikawa Medical College, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Chiba
authors.forename: M
authors.initials: M
authors.lastname: Ogasawara
authors.forename: I
authors.initials: I
authors.lastname: Yoshida
authors.forename: Y M
authors.initials: YM
authors.lastname: Knox
authors.forename: T
authors.initials: T
authors.lastname: Suzutani
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D003851:Deoxyribonucleases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; C044200:glycoprotein H, herpes simplex virus type 1; D003851:Deoxyribonucleases