Gelb L, Dohner D
J Invest Dermatol. 1984 Jul;83(1 Suppl):77s-81s. doi: 10.1111/1523-1747.ep12281388.
A mixture of varicella-zoster virus-infected human embryonic lung fibroblasts and hamster embryo cells produced foci of morphologically transformed cells after several weeks of incubation. These transformed cells exhibited virus-specific antigens by immunofluorescence and developed surface Fc receptors. They induced aggressive fibrosarcomas when injected back into inbred hamsters. Cells derived from hamster tumor tissue exhibited similar properties. The tumor-bearing hamsters develop antibodies specific for varicella-zoster virus (VZV) antigens. Cell lines derived from both the original transformants and explanted hamster tumor tissue have varying growth properties. All maintain indefinite growth. All eventually lose varicella-zoster virus-specific immunofluorescence. None retain VZV-specific DNA sequences as determined by dot blot and Southern blot hybridization using radiolabeled whole VZV DNA and cloned VZV DNA fragments as a probe. A few transformed and tumor cell lines frozen relatively soon after isolation and stored in liquid nitrogen were also thawed, replicated to mass culture, and analyzed for VZV-specific DNA sequences. Hybridization with radiolabeled whole VZV DNA initially suggested that some of these cell lines did contain virus-specific DNA sequences. However, hybridization with cloned VZV DNA fragments radiolabeled in vitro and representing greater than 95% of the virus genome was negative. Karyotyping of these "positive" transformed cells indicated that they are of human and not hamster origin. The positive hybridization with whole VZV DNA therefore most likely represented contamination of the probe by host DNA sequences. The cells that survived freezing then were predominantly transformants of human origin. Attempts to repeat the transformation of hamster embryo and baby hamster kidney cells with laboratory-passaged VZV strains have been unsuccessful. Similarly, we have been unable to transform cells with whole VZV DNA or cloned VZV DNA fragments, although whole VZV DNA is demonstrably infectious. Apparently, transformation of cells by the varicella-zoster virus is a very rare event and one that may require a recent clinical isolate. Fresh clinical isolates of varicella-zoster virus are seemingly able to transform mammalian cells in vitro. The transformed cells have malignant properties and are capable of indefinite growth. Although VZV gene function can be detected early after transformation, there is no evidence that a VZV-specific protein product is required. Transformation of mammalian cells by varicella-zoster virus apparently occurs through a "hit-and-run" mechanism.
将水痘 - 带状疱疹病毒感染的人胚肺成纤维细胞和仓鼠胚胎细胞的混合物培养数周后，产生了形态学上转化的细胞集落。这些转化细胞通过免疫荧光显示出病毒特异性抗原，并产生了表面Fc受体。当将它们重新注射到近交系仓鼠体内时，会诱发侵袭性纤维肉瘤。源自仓鼠肿瘤组织的细胞表现出类似的特性。荷瘤仓鼠产生了针对水痘 - 带状疱疹病毒（VZV）抗原的特异性抗体。源自原始转化细胞和移植的仓鼠肿瘤组织的细胞系具有不同的生长特性。所有细胞系都能无限生长。所有细胞系最终都失去了水痘 - 带状疱疹病毒特异性免疫荧光。使用放射性标记的完整VZV DNA和克隆的VZV DNA片段作为探针，通过斑点印迹和Southern印迹杂交测定，没有一个细胞系保留VZV特异性DNA序列。一些在分离后相对较早冷冻并保存在液氮中的转化细胞系和肿瘤细胞系也被解冻，扩增至大规模培养，并分析其VZV特异性DNA序列。与放射性标记的完整VZV DNA杂交最初表明，其中一些细胞系确实含有病毒特异性DNA序列。然而，与体外放射性标记的、代表病毒基因组95%以上的克隆VZV DNA片段杂交结果为阴性。对这些“阳性”转化细胞进行核型分析表明，它们是人源而非仓鼠源。因此，与完整VZV DNA的阳性杂交很可能是宿主DNA序列污染了探针所致。冷冻后存活的细胞主要是人源转化细胞。用实验室传代的VZV毒株重复转化仓鼠胚胎细胞和幼仓鼠肾细胞的尝试均未成功。同样，我们也无法用完整的VZV DNA或克隆的VZV DNA片段转化细胞，尽管完整的VZV DNA具有明显的感染性。显然，水痘 - 带状疱疹病毒对细胞的转化是一个非常罕见的事件，可能需要近期的临床分离株。水痘 - 带状疱疹病毒的新鲜临床分离株似乎能够在体外转化哺乳动物细胞。转化后的细胞具有恶性特性，能够无限生长。尽管在转化后早期可以检测到VZV基因功能，但没有证据表明需要VZV特异性蛋白质产物。水痘 - 带状疱疹病毒对哺乳动物细胞的转化显然是通过“打了就跑”机制发生的。
