The dynamics of human cytomegalovirus replication in vivo.
The dynamics of human cytomegalovirus replication in vivo.
复制标题
人类巨细胞病毒在体内复制的动力学。
DOI：
10.1084/jem.190.2.177
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发表时间：
1999-07-19
影响因子：
15.3
通讯作者：
Griffiths, P D
中科院分区：
文献类型：
--
作者：
Emery, V C;Cope, A V;Bowen, E F;Gor, D;Griffiths, P D
巨细胞病毒（CMV）通常被描述为缓慢复制的病毒。在免疫功能低下患者的研究中，我们通过定量竞争性聚合酶链反应观察到系列血液样本中CMV DNA数量的快速变化，倍增时间小于2 d。为了进一步研究体内复制的动力学，详细研究了三种不同情况下的患者：（a）接受静脉注射更昔洛韦的患者;（B）在长期治疗期间出现更昔洛韦耐药菌株的患者;以及（c）在替代药物治疗后更昔洛韦耐药菌株消失的患者。在所有情况下，都有可能提供准确的估计CMV的倍增时间和抗病毒化疗后消失的半衰期。所有三种方法的结果表明，当频繁采集样本时，血液中CMV的倍增时间/半衰期为101 d。这些结果表明，CMV DNA在体内复制是一个高度动态的过程。我们的结论是，CMV作为一种缓慢复制的病毒的声誉的基础上所需的时间，以产生细胞病变的影响，在体外是没有根据的。这些发现对有效治疗这种重要的人类病原体所需的抗病毒化疗的效力，剂量和持续时间具有影响。
Cytomegalovirus (CMV) is generally described as a slowly replicating virus. During studies of immunocompromised patients, we observed rapid changes in the quantity of CMV DNA present in serial blood samples by quantitative-competitive polymerase chain reaction commensurate with a doubling time of <2 d. To further investigate the dynamics of replication in vivo, patients in three distinct situations were studied in detail: (a) those receiving intravenous ganciclovir; (b) those in whom ganciclovir-resistant strains appeared during long-term therapy; and (c) those in whom ganciclovir-resistant strains disappeared with alternative drug therapy. In all cases, it was possible to provide accurate estimates of the doubling time of CMV and its half-life of disappearance after antiviral chemotherapy. The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is ∼1 d when frequent samples are collected. These results show that CMV DNA replication in vivo is a highly dynamic process. We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted. These findings have implications for the potency, dose, and duration of antiviral chemotherapy needed for the effective treatment of this important human pathogen.