Leibniz Institute for Experimental Virology, Department of Molecular Virology, Hamburg, Germany.
PLoS One. 2013 May 6;8(5):e63646. doi: 10.1371/journal.pone.0063646. Print 2013.
Human adenoviruses are known to persist in T-lymphocytes of tonsils, adenoids and intestinal tract. The oncogenic potential of different adenovirus types has been widely studied in rodents, in which adenovirus inoculation can induce multiple tumors such as undifferentiated sarcomas, adenocarcinomas and neuroectodermal tumors. However, the oncogenic potential of this virus has never been proven in human subjects. Using a highly sensitive broad-spectrum qRT-PCR, we have screened a set of different human sarcomas including leiomyosarcoma, liposarcoma and gastro intestinal stroma tumors. Primers binding the viral oncogene E1A and the capsid-coding gene Hexon were used to detect the presence of adenovirus DNA in tumor samples. We found that 18% of the tested leiomyosarcomas and 35% of the liposarcomas were positive for the presence of adenovirus DNA, being species C types the most frequently detected adenoviruses. However, only in one sample of the gastro intestinal stroma tumors the virus DNA could be detected. The occurrence of adenovirus in the tumor sections was confirmed by subsequent fluorescence in-situ-hybridization analysis and co-staining with the transcription factor Bcl11b gives evidence for the presence of the virus in infiltrating T-lymphocytes within the tumors. Together these data underline, for the first time, the persistence of adenovirus in T-lymphocytes infiltrated in muscular and fatty tissue tumor samples. If an impaired immune system leads to the viral persistence and reactivation of the virus is involved in additional diseases needs further investigation.
人类腺病毒已知存在于扁桃体、腺样体和肠道的 T 淋巴细胞中。不同腺病毒类型的致癌潜力已在啮齿动物中广泛研究,其中腺病毒接种可诱导多种肿瘤,如未分化肉瘤、腺癌和神经外胚层肿瘤。然而,该病毒的致癌潜力从未在人类受试者中得到证实。我们使用高度敏感的广谱 qRT-PCR 筛选了一组不同的人类肉瘤,包括平滑肌肉瘤、脂肪肉瘤和胃肠道间质瘤。结合病毒致癌基因 E1A 和衣壳编码基因 Hexon 的引物用于检测肿瘤样本中腺病毒 DNA 的存在。我们发现,18%的测试平滑肌肉瘤和 35%的脂肪肉瘤中存在腺病毒 DNA,其中 C 型腺病毒最为常见。然而,只有在一个胃肠道间质瘤样本中才能检测到病毒 DNA。通过随后的荧光原位杂交分析和与转录因子 Bcl11b 的共染色,证实了肿瘤切片中腺病毒的存在,这表明病毒存在于肿瘤浸润的 T 淋巴细胞中。这些数据首次强调了腺病毒在肌肉和脂肪组织肿瘤样本中浸润的 T 淋巴细胞中的持续存在。如果免疫系统受损导致病毒持续存在,病毒的重新激活是否涉及其他疾病需要进一步研究。