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在小鼠系统中,苏拉明对逆转录病毒传播和疾病的抑制作用。

Suppression of retroviral propagation and disease by suramin in murine systems.

作者信息

Ruprecht R M, Rossoni L D, Haseltine W A, Broder S

出版信息

Proc Natl Acad Sci U S A. 1985 Nov;82(22):7733-7. doi: 10.1073/pnas.82.22.7733.

Abstract

Retroviral propagation crucially depends on reverse transcriptase (RT). We have developed murine models to test the biological effectiveness of the RT inhibitor suramin. The drug was active in our assay system, which includes (i) inhibition of RT activity in the murine T-cell tropic virus SL3-3 and Rauscher murine leukemia virus (MuLV), (ii) inhibition of plaque formation in the XC plaque assay, (iii) inhibition of viral infection of cultured murine T cells, and (iv) inhibition of splenomegaly induced by Rauscher MuLV in BALB/c mice. Suramin decreases viral titers significantly, even if started 36 hr after infection. Viral titers and number of infected cells increased to control levels after removal of the drug. BALB/c mice treated i.v. with 40 mg of suramin per kg twice per week following infection with Rauscher MuLV showed a 35% decrease in splenomegaly. Suramin is an active antiretroviral agent whose effect on retroviral propagation is reversible. We conclude that it acts as a virustatic drug and that long-term administration of suramin will be necessary if it is used for experimental treatment of human retroviral illnesses such as the acquired immune deficiency syndrome.

摘要

逆转录病毒的增殖关键取决于逆转录酶(RT)。我们已开发出小鼠模型来测试RT抑制剂苏拉明的生物学有效性。该药物在我们的检测系统中具有活性,包括:(i)抑制鼠T细胞嗜性病毒SL3 - 3和劳舍尔小鼠白血病病毒(MuLV)中的RT活性;(ii)在XC空斑试验中抑制空斑形成;(iii)抑制培养的鼠T细胞的病毒感染;以及(iv)抑制劳舍尔MuLV在BALB/c小鼠中诱导的脾肿大。即使在感染后36小时开始使用,苏拉明也能显著降低病毒滴度。去除药物后,病毒滴度和感染细胞数量增加至对照水平。感染劳舍尔MuLV后,每周两次静脉注射40 mg/kg苏拉明治疗的BALB/c小鼠脾肿大减少了35%。苏拉明是一种有效的抗逆转录病毒药物,其对逆转录病毒增殖的作用是可逆的。我们得出结论,它作为一种病毒生长抑制剂发挥作用,如果将其用于人类逆转录病毒疾病如获得性免疫缺陷综合征的实验性治疗,长期使用苏拉明将是必要的。

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