Herpesvirus Alkaline Deoxyribonuclease; a Possible Candidate as a Novel Target for Anti-Herpesvirus Therapy
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ATSUSHI CHIBA, MASAHIRO OGASAWARA, ITSURO YOSHIDA, YOKO M. KNOX and TATSUO SUZUTANI
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Department of Microbiology, Asahikawa Medical College, Asahikawa 078-8510
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 anti-herpesvirus 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 mM, 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 mM of UL12-4, but no effect was observed on the quantity of HSV-1 glycoprotein H mRNA (g2 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.
Key words---
herpes simplex virus; alkaline DNase; antisense oligonucleotide
© 2000 Tohoku University Medical Press
Tohoku J. Exp. Med., 2000, 192, 141-149
Address for reprints: Tatsuo Suzutani, Department of Microbiology, Asahikawa Medical College, 2-1-1-1 Midorigaokahigashi, Asahikawa 078-8510, Japan.
e-mail: suzutani@asahikawa-med.ac.jp
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