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亚硒酸盐对柯萨奇病毒B5复制的抑制作用:对克山病病因学的启示

Selenite inhibition of Coxsackie virus B5 replication: implications on the etiology of Keshan disease.

作者信息

Cermelli Claudio, Vinceti Marco, Scaltriti Elisa, Bazzani Erika, Beretti Francesca, Vivoli Gianfranco, Portolani Marinella

机构信息

Dipartimento di Scienze Igienistiche, Microbiologiche e Biostatistiche, Università di Modena e Reggio Emilia, Italia.

出版信息

J Trace Elem Med Biol. 2002;16(1):41-6. doi: 10.1016/S0946-672X(02)80007-4.

DOI:10.1016/S0946-672X(02)80007-4
PMID:11878751
Abstract

Keshan disease is a cardiomyopathy of unknown origin reported in some areas of China. Because of epidemiologic features, this disease was ascribed to an infectious agent, likely a Coxsackie virus, but it has also been thought to depend on selenium deficiency, mainly because selenite is effective in its prophylaxis. We examined the hypothesis that pharmacological activity of selenite on Coxsackie virus growth was associated with prevention of Keshan disease. We studied the antiviral effects of three selenium compounds on Coxsackie virus B5 replication: five microM selenite reduced viral replication, whilst 10 microM selenate and selenomethionine did not exhibit any antiviral activity. The inhibitory activity of selenite on viral replication was due to its toxicity following its interaction with thiols, as that activity could be blocked by dithiothreitol, a sulfhydryl-protecting agent known to reverse several toxic effect of selenite. Zinc, another inhibitor of selenite toxicity, also counteracted the antiviral effect of selenite. The selenium compounds showed only limited activity against herpes simplex 1 virus and IHD strain of vaccinia virus. A direct inhibitory effect of selenite on Coxsackie virus replication might explain the efficacy demonstrated by this compound in the prophylaxis of Keshan disease.

摘要

克山病是一种在中国某些地区报道的病因不明的心肌病。由于其流行病学特征,该疾病被归因于一种感染因子,可能是柯萨奇病毒,但也有人认为它与硒缺乏有关,主要是因为亚硒酸盐对其预防有效。我们检验了亚硒酸盐对柯萨奇病毒生长的药理活性与预防克山病相关的假说。我们研究了三种硒化合物对柯萨奇病毒B5复制的抗病毒作用:5微摩尔的亚硒酸盐可减少病毒复制,而10微摩尔的硒酸盐和硒代蛋氨酸未表现出任何抗病毒活性。亚硒酸盐对病毒复制的抑制活性是由于其与硫醇相互作用后的毒性,因为该活性可被二硫苏糖醇阻断,二硫苏糖醇是一种已知可逆转亚硒酸盐多种毒性作用的巯基保护剂。锌,亚硒酸盐毒性的另一种抑制剂,也抵消了亚硒酸盐的抗病毒作用。这些硒化合物对单纯疱疹病毒1型和痘苗病毒IHD株仅表现出有限的活性。亚硒酸盐对柯萨奇病毒复制的直接抑制作用可能解释了该化合物在预防克山病方面所显示的功效。

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