1988 Fiscal Year Final Research Report Summary
Study on the DNA replication of herpes simplex virus
| Project/Area Number |
62480158
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Nagoya University school of Medicine |
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Principal Investigator |
NISHIYAMA Yukihiro Nagoya University School of Medicine, 医学部, 助教授 (60115615)
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| Co-Investigator(Kenkyū-buntansha) |
TSURUMI Tatsuya Nagoya University School of Medicine, 医学部, 講師 (90172072)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Herpes simplex virus / DNA replication / DNA topoisomerase / DNA合成阻害剤 |
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| Research Abstract |
The results of our experiments are summarized as follows.
1) The epipodophyllotoxin VP-16-213 and camptothecin have been shown to interfer with the functions of mammalian DNA topoisomerase II and I, respectively. Both inhibitors strongly suppressed the growth of herpes simplex virus. From our experiments using the two inhibitors, if was suggested that celluler DNA topoisomerase II and I are involved in the HSV replication; The former enzyme mainly plays a role in the viral DNA replication but the latter seems to primarily act at the level of transcription.
2) Aphidicolin-resistant or phosphonoacetic acid-resistant mutants of HSV have been isolated and characterized. The physical map limits for the Aph^r mutation were contained in a 1.1 Kbp region within the HSV DNA polymerase locus. It was shown that the Aph^r mutant polymerase had an amino acid substitution from a thyrosin to a histidine in the wellconserved region of the dna polymerase, DNA suggested that this region may form a domain that contains the binding-sites for substrates, PPi and aphidicolin.
3) We found that citrusinine-i, a new acridone alkaloid isolated from the root bark of citrus plant, inhibited HSV DNA synthesis at the concertrations that did not affect the synthesis of HSV-induced early proteins. Further studies will be required to determine the target of this compound.
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