A HERPES-SIMPLEX VIRUS RIBONUCLEOTIDE REDUCTASE DELETION MUTANT IS DEFECTIVE FOR PRODUCTIVE ACUTE AND REACTIVATABLE LATENT INFECTIONS OF MICE AND FOR REPLICATION IN MOUSE CELLS
A HERPES-SIMPLEX VIRUS RIBONUCLEOTIDE REDUCTASE DELETION MUTANT IS DEFECTIVE FOR PRODUCTIVE ACUTE AND REACTIVATABLE LATENT INFECTIONS OF MICE AND FOR REPLICATION IN MOUSE CELLS
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DOI：
10.1016/0042-6822(89)90244-4
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发表时间：
1989-11-01
期刊：
影响因子：
3.7
通讯作者：
COEN, DM
中科院分区：
文献类型：
--
作者：
JACOBSON, JG;LEIB, DA;COEN, DM
单纯疱疹病毒编码一种核糖核苷酸还原酶，该还原酶对于病毒在分裂细胞中的生长不是必需的，如37 ° C。这种酶已被提议作为抗病毒药物的靶点;其在这方面的效用可能取决于其在体内的重要性。为了测试病毒核糖核苷酸还原酶在哺乳动物宿主中的需求，我们测试了突变病毒，缺乏大部分编码核糖核苷酸还原酶大亚基的基因，在小鼠眼模型的发病机制和潜伏期，其中野生型病毒建立可再活化的潜伏感染后，在三叉神经节角膜接种。缺失突变体在眼睛和三叉神经节中急性复制的能力严重受损，并且未能建立可再活化的潜伏感染。相反，缺失序列被恢复的重组病毒对急性和潜伏感染都有能力。小鼠中缺失突变体的缺陷可能与其在38 ° C严重受损的生长有关。相对于在Vero细胞中的生长。这些结果表明，核糖核苷酸还原酶对于小鼠中的生产性急性和可再活化的潜伏感染以及在38 ℃下在小鼠细胞中的复制是关键的。并建议在判断这种酶作为抗病毒化疗靶点的效用时，从小鼠研究推断人类感染时应谨慎。
Herpes simplex virus encodes a ribonucleotide reductase that is not essential for virus growth in dividing cells as 37.degree.. This enzyme has been proposed as a target for antiviral drugs; its utility in this regard could depend upon its importance in vivo. To test the requirement of viral ribonucleotide reductase in a mammalian host, we tested a mutant virus, lacking most of the gene encoding the ribonucleotide reductase large subunit, in a mouse eye model of pathogenesis and latency where the wild-type virus establishes reactivatable latent infections in trigeminal ganglia following corneal inoculation. The deletion mutant was severely impaired in its ability to replicate acutely in the eye and in the trigeminal ganglion and failed to establish reactivatable latent infections. In contrast, a recombinant virus in which the deleted sequences were restored was competent for both acute and latent infections. The defects of the deletion mutant in the mouse may be related to its severely impaired growth at 38.degree. in mouse cells relative to its growth in Vero cells. These results indicate that ribonucleotide reductase is critical for productive acute and reactivatable latent infections in mice and replication in mouse cells at 38.degree. and suggest that caution be exercised in extrapolating from studies conducted in mice to human infections when judging the utility of this enzyme as a target for antiviral chemotherapy.