Influence of the viral regulatory region on tumor induction by simian virus 40 in hamsters.
Influence of the viral regulatory region on tumor induction by simian virus 40 in hamsters.
复制标题
病毒调节区对仓鼠中猿猴病毒 40 诱导肿瘤的影响。
DOI：
10.1128/jvi.01626-07
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发表时间：
2008
影响因子：
5.4
通讯作者：
Butel,JanetS
中科院分区：
文献类型：
--
作者：
Sroller,Vojtech;Vilchez,RegisA;Stewart,ARenee;Wong,Connie;Butel,JanetS
猿猴病毒40 （SV40）的大部分基因组在分离株中是保守的，但非编码调控区和编码大t抗原C端（T-ag-C）的基因组区可能表现出相当大的差异。我们在这里证明SV40分离物在叙利亚金仓鼠中的致癌潜力不同。实验动物腹腔注射107PFU亲本或重组SV40病毒，观察12个月，以确定致瘤性的遗传决定因素。研究发现，病毒调控区对肿瘤发病率的影响具有统计学意义，而T-ag-C的作用较小。具有单增强子（1E）结构的病毒比具有双增强子（2E）结构的病毒更具有致癌性。60例肿瘤中有4例（6.7%）检测到1E病毒调控区的重排。肿瘤中的病毒载量各不相同，每个细胞中位数为5.4 SV40基因组拷贝。37株（40%）肿瘤细胞系中有15株可获得传染性SV40。大多数有肿瘤的仓鼠和许多没有肿瘤的仓鼠产生针对T抗原的抗体。所有病毒在体外都显示出相似的转化频率，这表明体内致癌潜力的差异是由于宿主对病毒感染的反应。本研究表明SV40毒株在生物学特性上存在差异，表明SV40在仓鼠体内有一定程度的复制，并表明SV40感染的结果可能取决于存在的病毒毒株。
Most of the simian virus 40 (SV40) genome is conserved among isolates, but the noncoding regulatory region and the genomic region encoding the large T-antigen C terminus (T-ag-C) may exhibit considerable variation. We demonstrate here that SV40 isolates differ in their oncogenic potentials in Syrian golden hamsters. Experimental animals were inoculated intraperitoneally with 107PFU of parental or recombinant SV40 viruses and were observed for 12 months to identify genetic determinants of oncogenicity. The viral regulatory region was found to exert a statistically significant influence on tumor incidence, whereas the T-ag-C played a minor role. Viruses with a single enhancer (1E) were more oncogenic than those with a two-enhancer (2E) structure. Rearrangements in the 1E viral regulatory region were detected in 4 of 60 (6.7%) tumors. Viral loads in tumors varied, with a median of 5.4 SV40 genome copies per cell. Infectious SV40 was rescued from 15 of 37 (40%) cell lines established from tumors. Most hamsters with tumors and many without tumors produced antibodies to T antigen. All viruses displayed similar transforming frequencies in vitro, suggesting that differences in oncogenic potential in vivo were due to host responses to viral infection. This study shows that SV40 strains differ in their biological properties, suggests that SV40 replicates to some level in hamsters, and indicates that the outcome of an SV40 infection may depend on the viral strain present.