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白喉毒素活性的研究。I. 脊髓灰质炎病毒在中毒的海拉细胞中的复制。

Studies of the activity of diphtheria toxin. I. Poliovirus replication in intoxicated HeLa cells.

作者信息

Duncan J L, Groman N B

出版信息

J Exp Med. 1967 Mar 1;125(3):489-500. doi: 10.1084/jem.125.3.489.

DOI:10.1084/jem.125.3.489
PMID:4289295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2138288/
Abstract

It has been demonstrated that a saturating dose of diphtheria toxin produced a 90% inhibition of polio-virus replication in HeLa cells. This inhibition was reflected in infectious viral RNA synthesis and in mature virus production. Toxin had no direct effect on virus particles or I-RNA, and poliovirus adsorption and eclipse appeared to be carried out normally in intoxicated cells. When toxin was given at various time intervals after infection, the amount of inhibition depended on the time of toxin addition. Toxin given before or immediately after infection gave maximum inhibition, while toxin given several hours after infection had little effect. The data suggest that toxin inhibits viral replication through its effect on protein synthesis. It is likely that a critical step in the viral replication cycle, the production of poliovirus-induced RNA polymerase, is inhibited, and possibly the synthesis of capsid protein. Ammonium salts and the aliphatic amines, glycamine and prolamine, prevented the inhibition of viral replication by toxin. The kinetics of the protective action of ammonium chloride and diphtheria antitoxin are remarkably similar.

摘要

已经证明,饱和剂量的白喉毒素可使脊髓灰质炎病毒在HeLa细胞中的复制受到90%的抑制。这种抑制反映在感染性病毒RNA的合成以及成熟病毒的产生上。毒素对病毒颗粒或感染性RNA没有直接影响,并且脊髓灰质炎病毒的吸附和隐蔽期在中毒细胞中似乎正常进行。当在感染后的不同时间间隔给予毒素时,抑制程度取决于毒素添加的时间。在感染前或感染后立即给予毒素可产生最大抑制,而在感染数小时后给予毒素则几乎没有效果。数据表明,毒素通过对蛋白质合成的影响来抑制病毒复制。病毒复制周期中的一个关键步骤,即脊髓灰质炎病毒诱导的RNA聚合酶的产生可能受到抑制,衣壳蛋白的合成也可能受到抑制。铵盐以及脂肪族胺类、甘胺和谷胺可防止毒素对病毒复制的抑制。氯化铵和白喉抗毒素的保护作用动力学非常相似。

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引用本文的文献

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Activity of diphtheria toxin. II. Early events in the intoxication of HeLa cells.白喉毒素的活性。II. 海拉细胞中毒的早期事件。
J Bacteriol. 1969 Jun;98(3):963-9. doi: 10.1128/jb.98.3.963-969.1969.
2
Response of cultured mammalian cells to diphtheria toxin. 3. Inhibition of protein synthesis studied at the subcellular level.培养的哺乳动物细胞对白喉毒素的反应。3. 在亚细胞水平研究蛋白质合成的抑制作用。
J Bacteriol. 1968 Jul;96(1):61-9. doi: 10.1128/jb.96.1.61-69.1968.
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Heat-activated endonuclease in Bacillus subtilis.枯草芽孢杆菌中的热激活核酸内切酶。
J Bacteriol. 1969 Mar;97(3):1426-30. doi: 10.1128/jb.97.3.1426-1430.1969.
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Studies on the mode of action of diphtheria toxin. 3. Site of toxin action in cell-free extracts.白喉毒素作用方式的研究。3. 毒素在无细胞提取物中的作用位点。
J Exp Med. 1967 Nov 1;126(5):899-912. doi: 10.1084/jem.126.5.899.
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Uptake of diphtheria toxin and its fragment A moiety by mammalian cells in culture.培养的哺乳动物细胞对白喉毒素及其A片段的摄取。
Infect Immun. 1976 Sep;14(3):742-51. doi: 10.1128/iai.14.3.742-751.1976.
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Diphtheria toxin: mode of action and structure.白喉毒素:作用方式与结构
Bacteriol Rev. 1975 Mar;39(1):54-85. doi: 10.1128/br.39.1.54-85.1975.

本文引用的文献

1
Improved method for staining cell monolayers for virus plaque counts.用于病毒蚀斑计数的细胞单层染色改进方法。
J Bacteriol. 1959 Oct;78(4):596-7. doi: 10.1128/jb.78.4.596-597.1959.
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STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN. II. EFFECT OF TOXIN ON AMINO ACID INCORPORATION IN CELL-FREE SYSTEMS.白喉毒素作用方式的研究。II. 毒素对无细胞体系中氨基酸掺入的影响。
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IN VITRO SYNTHESIS OF VIRAL RNA BY THE POLIOVIRUS RNA POLYMERASE.脊髓灰质炎病毒RNA聚合酶在体外合成病毒RNA
Proc Natl Acad Sci U S A. 1964 Mar;51(3):450-6. doi: 10.1073/pnas.51.3.450.
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Poliovirus-induced RNA polymerase and the effects of virus-specific inhibitors on its production.脊髓灰质炎病毒诱导的RNA聚合酶及其病毒特异性抑制剂对其产生的影响。
Proc Natl Acad Sci U S A. 1963 Jun;49(6):843-9. doi: 10.1073/pnas.49.6.843.
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Early stages of enterovirus infection.肠道病毒感染的早期阶段。
Cold Spring Harb Symp Quant Biol. 1962;27:101-12. doi: 10.1101/sqb.1962.027.001.013.
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Irreversible eclipse of poliovirus by HeLa cells.脊髓灰质炎病毒被海拉细胞不可逆地抑制。
Virology. 1962 Feb;16:163-76. doi: 10.1016/0042-6822(62)90292-1.
7
An early effect of diphtheria toxin on the metabolism of mammalian cells growing in culture.白喉毒素对培养中的哺乳动物细胞代谢的早期影响。
J Exp Med. 1960 Aug 1;112(2):329-49. doi: 10.1084/jem.112.2.329.
8
The time course of synthesis of poliovirus RNA.脊髓灰质炎病毒RNA的合成时间进程。
Virology. 1961 Mar;13:271-9. doi: 10.1016/0042-6822(61)90145-3.
9
Enteroviral ribonucleic acid. I. Recovery from virus and assimilation by cells.肠道病毒核糖核酸。I. 从病毒中回收及被细胞摄取。
J Exp Med. 1960 Nov 1;112(5):821-39. doi: 10.1084/jem.112.5.821.
10
The effect of diphtheria toxin on the metabolism of HeLa cells.白喉毒素对海拉细胞代谢的影响。
J Exp Med. 1959 Feb 1;109(2):145-63. doi: 10.1084/jem.109.2.145.