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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation
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Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation

机译：疱疹病毒保守的UL97激酶在巨细胞病毒DNA合成和衣壳化中的不同作用

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摘要

The human cytomegalovirus UL97 kinase, an important target of antiviral therapy, has an impact on at least two distinct phases of viral replication. Compared with wild-type virus, the UL97 deletion mutant exhibits an early replication defect that reduces DNA accumulation by 4- to 6-fold, as well as a late capsid maturation defect responsible for most of the observed 100- to 1000-fold reduction in replication. Block-release experiments with the anti- viral 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)-benzimidazole re- vealed an important role for UL97 kinase in capsid assembly. Although cleavage of concatemeric DNA intermediates to unit- length genomes remained unaffected, progeny mutant virus mat- uration was delayed, with accumulation of progeny at significantly reduced levels compared with wild type after release of this block. Transmission electron microscopy confirmed the aberrant accumu- lation of empty A-like capsids containing neither viral DNA nor an internal scaffold structure, consistent with a failure to stably package DNA in mutant virus-infected cells. The function of UL97 in DNA synthesis as well as capsid assembly suggests that protein phosphorylation mediated by this herpesvirus-conserved kinase increases the efficiency of these two distinct phases of virus replication.
机译：人类巨细胞病毒UL97激酶是抗病毒治疗的重要目标，它对病毒复制的至少两个不同阶段具有影响。与野生型病毒相比，UL97缺失突变体表现出早期复制缺陷，使DNA积累减少了4到6倍，而衣壳成熟后期的缺陷导致了大多数观察到的100到1000倍的减少。复制。抗病毒2-溴-5,6-二氯-1-（β-D-呋喃呋喃糖基）-苯并咪唑的阻滞释放实验揭示了衣壳装配过程中UL97激酶的重要作用。尽管连接蛋白DNA中间体对单位长度基因组的切割仍然不受影响，但后代突变病毒的成熟被延迟了，与释放野生型相比，后代的积累水平大大低于野生型。透射电子显微镜证实，既不包含病毒DNA也不包含内部支架结构的空A样衣壳的异常积累，与未能将DNA稳定包装在被病毒感染的突变细胞中一致。 UL97在DNA合成以及衣壳装配中的功能表明，由这种疱疹病毒保守的激酶介导的蛋白质磷酸化提高了病毒复制这两个不同阶段的效率。

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