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首页> 外文期刊>Antiviral chemistry & chemotherapy >Antiviral activities and phosphorylation of 5-halo-2'-deoxyuridines and N-methanocarbathymidine in cells infected with vaccinia virus.
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Antiviral activities and phosphorylation of 5-halo-2'-deoxyuridines and N-methanocarbathymidine in cells infected with vaccinia virus.

机译：在牛痘病毒感染的细胞中，5-卤代2'-脱氧尿苷和N-甲氨基甲氧嘧啶的抗病毒活性和磷酸化。

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BACKGROUND: The antipoxviral activities and phosphorylation of N-methanocarbathymidine ([N]-MCT) and four 5-halo-2'-deoxyuridines, namely 5-fluoro-(FdU), 5-chloro-(CldU), 5-bromo-(BrdU), and 5-iodo-(IdU) derivatives, were explored. METHODS: Antiviral activities and nucleoside metabolism were determined in C127I mouse, LLC-MK2 monkey, and A549 human cells infected with thymidine-kinase-containing and -deficient (TK+ and TK-) vaccinia (WR strain) viruses. RESULTS: The antiviral potencies of CldU, BrdU and IdU were increased 16-26-fold in LLC-MK2 cells infected with TK+ compared with TK- virus infections, but enhancement of activity was much less in the other cell lines. (N)-MCT was nearly equally active against TK+ and TK- viruses in the three cell lines. Antiviral activity of FdU was associated with cytotoxicity. Uninfected and infected cells metabolized compounds to mono-, di- and triphosphates. The thymidine, BrdU and IdU triphosphate levels were higher in C127I and LLC-MK2 cells infected with TK+ than with TK- virus. (N)-MCT monophosphate levels were much higher in TK+ virus-infected cells, but without corresponding increases in (N)-MCT triphosphate. Furthermore, TK+ virus infections did not appreciably alter (N)-MCT triphosphate levels in other mouse (L929), monkey (MA-104 and Vero) and human cell lines (A549). Antiviral potency of the compounds was greater in C127I than in LLC-MK2 cells, yet lower intracellular triphosphate levels were found in C127I cells. CONCLUSION: We conclude that viral TK plays an important role in increasing the antiviral potencies of these compounds in some cell lines, but minimally in others. These findings may have implications in treating infected animals with compounds that are dependent upon poxvirus TK for their activation, because viral TK activity may vary greatly due to cell type.
机译：背景：N-甲氨基碳吡啶（[N] -MCT）和四个5-卤代2'-脱氧尿苷，即5-氟-（FdU），5-氯-（CldU），5-溴-探索了（BrdU）和5-碘-（IdU）衍生物。方法：测定感染了含胸苷激酶和缺陷型（TK +和TK-）牛痘（WR株）病毒的C127I小鼠，LLC-MK2猴和A549人细胞的抗病毒活性和核苷代谢。结果：与TK病毒感染相比，用TK +感染的LLC-MK2细胞的CldU，BrdU和IdU的抗病毒能力提高了16-26倍，但在其他细胞系中活性的增强却很少。 （N）-MCT在这三种细胞系中对TK +和TK-病毒的活性几乎相同。 FdU的抗病毒活性与细胞毒性有关。未感染和感染的细胞将化合物代谢为单磷酸，二磷酸和三磷酸。在用TK +感染的C127I和LLC-MK2细胞中，胸苷，BrdU和IdU三磷酸水平更高，而在TK-病毒中则更高。 （N）-MCT单磷酸水平在TK +病毒感染的细胞中要高得多，但（N）-MCT三磷酸水平却没有相应的增加。此外，TK +病毒感染并未明显改变其他小鼠（L929），猴（MA-104和Vero）和人细胞系（A549）中的（N）-MCT三磷酸水平。该化合物的抗病毒效力在C127I中比在LLC-MK2细胞中更高，但在C127I细胞中发现较低的细胞内三磷酸水平。结论：我们得出结论，病毒TK在增加某些化合物中这些化合物的抗病毒效力中起着重要作用，而在另一些细胞系中则起着很小的作用。这些发现可能对用依赖于痘病毒TK活化的化合物治疗感染的动物有影响，因为病毒TK活性可能因细胞类型而有很大差异。

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