ANABOLIC PATHWAY OF 6-METHOXYPURINE ARABINOSIDE IN CELLS INFECTED WITH VARICELLA-ZOSTER VIRUS

被引:6
作者
DEMIRANDA, P
BURNETTE, TC
BIRON, KK
MILLER, RL
AVERETT, DR
KRENITSKY, TA
机构
[1] Wellcome Research Laboratories, Res. Triangle Park
关键词
D O I
10.1128/AAC.35.10.2121
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
6-Methoxypurine arabinoside (ara-M) exhibits potent activity against varicella-zoster virus (VZV) as a result of ara-M's anabolism to the triphosphate of adenine arabinoside (ara-ATP) in VZV-infected cells. The adenosine deaminas inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) enhanced the formation of ara-ATP by inhibiting ara-M demethoxylation. In contrast, deoxycoformycin and coformycin, inhibitors of both adenosine deaminase and AMP deaminase, blocked the formation of ara-ATP and reversed the anti-VZV activity of ara-M. These results indicate that after the initial phosphorylation of ara-M by the VZV-coded thymidine kinase, the monophosphate is demethoxylated by AMP deaminase to form ara-IMP, which is converted to ara-ATP by the sequential actions of the cellular adenylosuccinate synthetase, adenylosuccinate lyase, and nucleotide kinases.
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页码:2121 / 2124
页数:4
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