Wirth J J, Martin L G, Fluck M M
Department of Microbiology, Michigan State University, East Lansing, USA.
J Virol. 1997 Feb;71(2):1072-8. doi: 10.1128/JVI.71.2.1072-1078.1997.
A correlation between polyomavirus-induced oncogenesis and viral persistence on the one hand and/or prolonged genome replication potential on the other was established with respect to their respective organ distributions. Prolonged replication potential is defined as the capacity of a genome to replicate in a given organ from the time of infection up to the onset of oncogenesis. This conclusion was derived following intraperitoneal infection of BALB/c mice with wild-type strain A2. Viral genomes were used as parameters of persistence and replication and were detected by Southern blotting and PCR analysis. The major tumor target organs (mammary gland, skin, and bone), which have not been previously analyzed for persistence, were compared with other, non-tumor-prone organs (kidney, liver, lung, spleen, and salivary gland). A progressive loss of viral genomes was observed in all tissues as a function of time postinfection; however, genomes were shown to persist through 20 weeks postinfection in the mammary glands, skin, and bones to an extent similar to that in the previously described kidneys (D. J. McCance, J. Virol. 39:958-962, 1981; W. P. Rowe, J. W. Hartley, J. D. Estes, and R. J. Huebner, Natl. Cancer Inst. Monogr. 4:189-209, 1960). Thus, tumors arise among organs that sustain a persistent infection, but not all such organs develop tumors (e.g., the kidney). The capacity of organs to support de novo replication at various ages, including the age reached when the first tumors are detected, was also determined using a 3-day infection period for ages between 0 and 7 weeks. For all organs tested, a higher level of genomes was observed in organs of mice infected as neonates than in those infected after the age of 3 weeks. However, marked organ-specific differences were seen in the degree and timing of loss of replication. In particular, viral genome replication, although reduced, was maintained in the mammary glands, skin, and bones of adult animals, in contrast to the kidneys. We conclude that organ-specific oncogenesis correlates with two organ-specific parameters: persistence of viral genomes and prolonged viral genome replication potential. This may reflect a requirement for continued viral genome replication and/or gene expression for tumorigenesis. In turn, these parameters may be linked to the tissue-specific continued capacity for cellular division.
就多瘤病毒诱导的肿瘤发生与病毒持续性以及/或者延长的基因组复制潜能之间的相关性而言，已根据它们各自的器官分布得以确立。延长的复制潜能被定义为基因组从感染之时直至肿瘤发生开始在给定器官中进行复制的能力。这一结论是在用野生型A2毒株对BALB/c小鼠进行腹腔感染之后得出的。病毒基因组被用作持续性和复制的参数，并通过Southern印迹法和PCR分析进行检测。将此前未针对持续性进行分析的主要肿瘤靶器官（乳腺、皮肤和骨骼）与其他不易发生肿瘤的器官（肾脏、肝脏、肺、脾脏和唾液腺）进行了比较。随着感染后时间的推移，在所有组织中均观察到病毒基因组的逐渐丢失；然而，在乳腺、皮肤和骨骼中，病毒基因组在感染后20周仍持续存在，其程度与先前描述的肾脏中的情况相似（D. J. McCance，《病毒学杂志》39:958 - 962，1981；W.P. Rowe、J.W. Hartley、J.D. Estes和R.J. Huebner，《国立癌症研究所专论》4:189 - 209，1960）。因此，肿瘤在维持持续性感染的器官中出现，但并非所有此类器官都会发生肿瘤（例如肾脏）。还使用了为期3天的感染期，对0至7周龄之间的小鼠进行检测，以确定各器官在不同年龄，包括首次检测到肿瘤时所达到的年龄，支持从头复制的能力。对于所有测试器官，在新生期感染的小鼠器官中观察到的基因组水平高于3周龄后感染的小鼠。然而，在复制丧失的程度和时间方面存在明显的器官特异性差异。特别是，与肾脏不同，成年动物乳腺、皮肤和骨骼中的病毒基因组复制虽然减少，但仍得以维持。我们得出结论，器官特异性肿瘤发生与两个器官特异性参数相关：病毒基因组的持续性和延长的病毒基因组复制潜能。这可能反映了肿瘤发生对病毒基因组持续复制和/或基因表达的需求。反过来，这些参数可能与组织特异性的细胞持续分裂能力相关。
