Photoreactivation of herpes simplex virus in human fibroblasts
Photoreactivation of herpes simplex virus in human fibroblasts
复制标题
人成纤维细胞中单纯疱疹病毒的光再激活
作者：
E. Wagner;M. Rice;B. Sutherland
当用紫外线（220-300 nm）处理DNA时，DNA 1链上相邻的嘧啶之间会产生环丁基嘧啶二聚体。这些二聚体是紫外线照射后简单生物体突变和死亡的主要原因1，并且它们与人类皮肤癌的诱导有关2，3。评估二聚体有害影响的一个重要工具是光复活试验：光复活酶通过在光依赖性（> 300 nm）反应中特异性和排他性的二聚体单体化来修复DNA 4，5。如果紫外线生物损伤可以通过真正的光酶修复来逆转，那么二聚体在该损伤的产生中起主要作用6。为了评估紫外线诱导的二聚体在人类致癌作用中的作用，至少必须满足三个标准：（1）人类细胞必须具有功能性光活化酶，（2）这种酶必须能够使DNA中的二聚体单体化，（3）这种酶必须能够恢复紫外线照射的DNA的生物活性。它已被证明，人类细胞满足前两个标准7，8;我们现在表明，人的光复活酶在成纤维细胞可以恢复感染性紫外线照射单纯疱疹病毒（HSV）。
WHEN DNA is treated with ultraviolet light (220–300 nm) cyclobutyl pyrimidine dimers are produced between adjacent pyrimidines on a strand of DNA1. These dimers are a major cause of mutations and death in simple organisms after ultraviolet-irradiation1, and they have been implicated in the induction of skin cancer in man2,3. An important tool for assessing the deleterious effects of dimers is the photoreactivation test: the photoreactivating enzyme repairs DNA by the specific and exclusive monomerisation of dimers in a light-dependent (> 300nm) reaction4,5. If ultraviolet biological damage can be reversed by true photoenzymatic repair, then dimers have a major role in the production of that damage6. For the test to assess the role of ultraviolet-induced dimers in human carcinogenesis at least three criteria must be met: (1) human cells must possess a functional photoreactivating enzyme, (2) this enzyme must be able to monomerise dimers in DNA, and (3) the enzyme must be able to restore biological activity to ultraviolet-irradiated DNA. It has been shown that human cells meet the first two criteria7,8; we now show that human photoreactivating enzyme in fibroblasts can restore infectivity to ultraviolet-irradiated herpes simplex virus (HSV).