Viral Mutation Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
Science. 2011 Jul 1;333(6038):97-101. doi: 10.1126/science.1205292. Epub 2011 May 31.
The retrovirus XMRV (xenotropic murine leukemia virus-related virus) has been detected in human prostate tumors and in blood samples from patients with chronic fatigue syndrome, but these findings have not been replicated. We hypothesized that an understanding of when and how XMRV first arose might help explain the discrepant results. We studied human prostate cancer cell lines CWR22Rv1 and CWR-R1, which produce XMRV virtually identical to the viruses recently found in patient samples, as well as their progenitor human prostate tumor xenograft (CWR22) that had been passaged in mice. We detected XMRV infection in the two cell lines and in the later passage xenografts, but not in the early passages. In particular, we found that the host mice contained two proviruses, PreXMRV-1 and PreXMRV-2, which share 99.92% identity with XMRV over >3.2-kilobase stretches of their genomes. We conclude that XMRV was not present in the original CWR22 tumor but was generated by recombination of two proviruses during tumor passaging in mice. The probability that an identical recombinant was generated independently is negligible (~10(-12)); our results suggest that the association of XMRV with human disease is due to contamination of human samples with virus originating from this recombination event.
逆转录病毒 XMRV（嗜性鼠白血病病毒相关病毒）已在人类前列腺肿瘤和慢性疲劳综合征患者的血液样本中被检测到，但这些发现尚未得到复制。我们假设，了解 XMRV 最初是何时以及如何出现的，可能有助于解释这些相互矛盾的结果。我们研究了人类前列腺癌细胞系 CWR22Rv1 和 CWR-R1，它们产生的 XMRV 与最近在患者样本中发现的病毒几乎完全相同，以及它们的祖先生殖细胞系 CWR22 （已在小鼠中传代）。我们在这两种细胞系和随后的传代异种移植中检测到了 XMRV 感染，但在早期传代中没有检测到。特别是，我们发现宿主小鼠含有两个前病毒，PreXMRV-1 和 PreXMRV-2，它们与 XMRV 在基因组的>3.2 千碱基长度上具有 99.92%的同一性。我们得出结论，XMRV 最初并不存在于原始的 CWR22 肿瘤中，而是在肿瘤在小鼠中传代过程中由两个前病毒的重组产生的。产生相同重组体的概率可以忽略不计（~10(-12)）；我们的结果表明，XMRV 与人类疾病的关联是由于人类样本受到源自这种重组事件的病毒污染。
