Abramczuk J, Pan S, Maul G, Knowles B B
J Virol. 1984 Feb;49(2):540-8. doi: 10.1128/JVI.49.2.540-548.1984.
Simian virus 40 (SV40), which transforms mouse cells in vitro, has not been previously observed to cause tumors when injected in immunocompetent mice. We have investigated both the fate of the injected virion in mice and several immunological parameters as potential factors controlling tumorigenicity. We find that although SV40 does not replicate in mouse cells, the viral DNA can persist for many months postinjection; the majority of the viral DNA is found in the cytoplasm, but a small amount of the viral DNA is integrated at multiple sites in the host nuclear DNA. The persistence of the viral genome is independent of the ability of the mouse to mount an SV40 TSTA specific cytotoxic T-cell response and may be attributed to the cytoplasmic location of the majority of the viral genome. However, in long-term studies of SV40-injected mice, genetically identical except for the major histocompatibility complex, we find that tumors were induced in some mice of the H-2d (low cytotoxic T-lymphocyte responder to SV40 TSTA) but not of the H-2k (high responder to SV40 TSTA) haplotype. Thus, a combination of inefficient disposal of the injected virion and inefficient immunological surveillance and elimination of cells containing nuclear SV40 DNA can eventually result in SV40-induced tumors at multiple sites in mice.
猴病毒40（SV40）在体外可转化小鼠细胞，但此前未观察到将其注射到具有免疫能力的小鼠体内会引发肿瘤。我们研究了注射的病毒粒子在小鼠体内的命运以及几个免疫参数，将其作为控制致瘤性的潜在因素。我们发现，尽管SV40不在小鼠细胞中复制，但病毒DNA在注射后可持续存在数月；大部分病毒DNA存在于细胞质中，但少量病毒DNA整合到宿主核DNA的多个位点。病毒基因组的持续存在与小鼠产生SV40肿瘤特异性移植抗原（TSTA）特异性细胞毒性T细胞反应的能力无关，这可能归因于大部分病毒基因组位于细胞质中。然而，在对注射了SV40的小鼠进行的长期研究中，这些小鼠除主要组织相容性复合体外基因相同，我们发现H-2d单倍型（对SV40 TSTA的细胞毒性T淋巴细胞反应较弱）的一些小鼠诱发了肿瘤，而H-2k单倍型（对SV40 TSTA反应较强）的小鼠则未诱发肿瘤。因此，注射的病毒粒子处理效率低下以及免疫监视和清除含有核SV40 DNA的细胞效率低下，最终可能导致小鼠多个部位出现SV40诱导的肿瘤。
