Interferon and its inducers - A never-ending story: "Old" and "new" data in a new perspective
Interferon and its inducers - A never-ending story: "Old" and "new" data in a new perspective
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DOI：
10.1086/505351
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发表时间：
2006-09-15
影响因子：
6.4
通讯作者：
De Clercq, Erik
中科院分区：
文献类型：
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作者：
De Clercq, Erik
干扰素（IFN）是一种抗病毒物质，由Isaacs和Lindenmann于1957年发现，引起了许多研究者的注意，包括比利时鲁汶Rega研究所的Pieter De Somer和斯坦福大学（加利福尼亚州）的Tom Merigan。De Somer最初的尝试旨在确定IFN b[2]的作用模式，而Merigan的工作重点是试图通过使用小鼠作为动物模型来了解IFN在人类病毒性疾病b[3]中的作用。具有开创性意义的是1967年Merigan b[4]证明，IFN可以通过一种称为马来二乙烯基醚共聚物（或吡喃共聚物）的合成阴离子诱导小鼠。在进一步的实验中，吡喃共聚物也被证明可以诱导人体内的IFN，尽管在人体内获得的血清IFN滴度远低于小鼠，而且伴随着体温的显著升高。同时，在De Somer的实验室中，我已经确定了另外两种聚阴离子，聚丙烯酸（PAA）和聚甲基丙烯酸作为抗病毒药物[6,7]，并将其抗病毒作用归因于诱导IFN或直接干扰病毒对细胞的吸附。总体而言，PAA和聚甲基丙烯酸的结构与吡喃共聚物非常相似（图1），突出的特征是cccccc -或cccccc -主链和带负电的羧酸安装在主链上。
The discovery of interferon (IFN), as an antiviral substance, by Isaacs and Lindenmann in 1957 [1] attracted the attention of a number of investigators, including Pieter De Somer at the Rega Institute in Leuven (Belgium) and Tom Merigan at Stanford University (California). De Somer’s original attempts were aimed at determining the mode of action of IFN [2], whereas Merigan’s work focused on trying to understand the role of IFN in human viral diseases [3], by use of the mouse as an animal model. Of pioneering importance was the demonstration by Merigan [4] in 1967 that IFN could be induced in mice by a synthetic polyanion called maleic divinyl ether copolymer (or pyran copolymer). In further experiments, pyran copolymer was also shown to induce IFN in humans [5], although the serum IFN titers obtained in humans were considerably lower than those in mice and, moreover, were accompanied by a considerable increase in body temperature. Meanwhile, in De Somer’s laboratory, I had identified 2 other polyanions, polyacrylic acid (PAA) and polymethacrylic acid, as antiviral agents [6, 7] and attributed their antiviral action to either the induction of IFN or a direct interference with virus adsorption to the cells. Overall, the structures of PAA and polymethacrylic acid are quite similar to that of pyran copolymer (figure 1), the prominent features being the-CCCCCC-or-CCCOCC-backbone and the negatively charged carboxylic acids mounted on this backbone.