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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Sensitivity of monkey B virus (Cercopithecine herpesvirus 1) to antiviral drugs: role of thymidine kinase in antiviral activities of substrate analogs and acyclonucleosides.
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Sensitivity of monkey B virus (Cercopithecine herpesvirus 1) to antiviral drugs: role of thymidine kinase in antiviral activities of substrate analogs and acyclonucleosides.

机译：猴B病毒（Cercopithecine疱疹病毒1）对抗病毒药的敏感性：胸苷激酶在底物类似物和无环核苷的抗病毒活性中的作用。

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摘要

Herpes B virus (B virus [BV]) is a macaque herpesvirus that is occasionally transmitted to humans where it can cause rapidly ascending encephalitis that is often fatal. To understand the low susceptibility of BV to the acyclonucleosides, we have cloned, expressed, and characterized the BV thymidine kinase (TK), an enzyme that is expected to "activate" nucleoside analogs. This enzyme is similar in sequence and properties to the TK of herpes simplex virus (HSV), i.e., it has a broad substrate range and low enantioselectivity and is sensitive to inhibitors of HSV TKs. The BV enzyme phosphorylates some modified nucleosides and acyclonucleosides and l enantiomers of thymidine and related antiherpetic analogs. However, the potent anti-HSV drugs acyclovir (ACV), ganciclovir (GCV), and 5-bromovinyldeoxyuridine were poorly or not phosphorylated by the BV enzyme under the experimental conditions. The antiviral activities of a number of marketed antiherpes drugs and experimental compounds were compared against BVstrains and, for comparison, HSV type 1 (HSV-1) in Vero cell cultures. For most compounds tested, BV was found to be about as sensitive as HSV-1 was. However, BV was less sensitive to ACV and GCV than HSV-1 was. The abilities of thymidine analogs and acyclonucleosides to inhibit replication of BV in Vero cell culture were not always proportional to their substrate properties for BV TK. Our studies characterize BV TK for the first time and suggest new lead compounds, e.g., 5-ethyldeoxyuridine and pencyclovir, which may be superior to ACV or GCV as treatment for this emerging infectious disease.
机译：乙型疱疹病毒（B病毒[BV]）是一种猕猴疱疹病毒，偶尔会传播给人类，在此会引起快速上升的脑炎，这通常是致命的。为了了解BV对无环核苷的低敏感性，我们克隆，表达和表征了BV胸苷激酶（TK），该酶有望“激活”核苷类似物。该酶的序列和性质与单纯疱疹病毒（HSV）的TK相似，即，它具有广泛的底物范围和低对映选择性，并且对HSV TK的抑制剂敏感。 BV酶使胸苷和相关的抗疱疹类似物的一些修饰的核苷和无环核苷以及l对映体磷酸化。但是，在实验条件下，有效的抗HSV药物阿昔洛韦（ACV），更昔洛韦（GCV）和5-溴乙烯基脱氧尿苷很难或不被BV酶磷酸化。比较了许多市售的抗疱疹药物和实验化合物的抗病毒活性与BV株，并比较了Vero细胞培养物中的HSV 1型（HSV-1）。对于大多数测试化合物，发现BV与HSV-1一样敏感。但是，与HSV-1相比，BV对ACV和GCV的敏感性较低。胸苷类似物和无环核苷抑制Vero细胞培养中BV复制的能力并不总是与它们对BV TK的底物特性成正比。我们的研究首次对BV TK进行了表征，并提出了新的先导化合物，例如5-乙基脱氧尿苷和Pencyclovir，它们可能优于ACV或GCV作为这种新兴传染病的治疗方法。

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