Lukacher A E, Freund R, Carroll J P, Bronson R T, Benjamin T L
Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115.
Virology. 1993 Sep;196(1):241-8. doi: 10.1006/viro.1993.1472.
Results in a previous report established the presence of dominant genetic factor(s) in C3H/BiDa mice which contributed to the unusually high susceptibility of this strain to polyoma virus-induced tumors (Freund et al. (1992) Virology 191, 724-731). Here we show that C57BR/cdJ mice, while identical to C3H/BiDa at the H-2 locus, are almost completely lacking in susceptibility. Analysis of crosses between these two H-2k strains has shown that susceptibility is due to a single dominant autosomal gene, designated Pyvs. On an H-2k background, Pyvs acts in a highly penetrant manner to confer susceptibility to induction of a broad range of tumors by the virus. Analysis of F1 mice between C3H/BiDa and the highly resistant C57BL/6 (H-2b) strain shows that Pyvs can partially overcome the immunologically mediated resistance associated with an H-2b haplotype. Pyvs does not encode cell receptors for the virus, nor does it affect levels of virus replication or anti-viral humoral responses in the host. Studies with early passage embryo fibroblasts in culture show that Pyvs does not affect intracellular events essential for either productive infection or cell transformation by the virus. Pyvs thus determines a generalized susceptibility of the host to polyoma-induced tumors but apparently does not act at the level of target cells for tumor induction.
先前一份报告的结果证实，C3H/BiDa小鼠中存在显性遗传因子，这导致该品系对多瘤病毒诱导的肿瘤异常易感（Freund等人，(1992) 《病毒学》191, 724 - 731）。在此我们表明，C57BR/cdJ小鼠虽然在H - 2位点与C3H/BiDa相同，但几乎完全缺乏易感性。对这两种H - 2k品系之间杂交的分析表明，易感性归因于一个单一的显性常染色体基因，命名为Pyvs。在H - 2k背景下，Pyvs以高度显性的方式起作用，使宿主对该病毒诱导的多种肿瘤易感。对C3H/BiDa和高度抗性的C57BL/6（H - 2b）品系之间的F1小鼠分析表明，Pyvs可以部分克服与H - 2b单倍型相关的免疫介导抗性。Pyvs不编码病毒的细胞受体，也不影响病毒在宿主体内的复制水平或抗病毒体液反应。对早期传代培养的胚胎成纤维细胞的研究表明，Pyvs不影响病毒进行有效感染或细胞转化所必需的细胞内事件。因此，Pyvs决定了宿主对多瘤病毒诱导肿瘤的普遍易感性，但显然不在肿瘤诱导的靶细胞水平起作用。
