Contreras-Galindo Rafael, Kaplan Mark H, Leissner Philippe, Verjat Thibault, Ferlenghi Ilaria, Bagnoli Fabio, Giusti Fabiola, Dosik Michael H, Hayes Daniel F, Gitlin Scott D, Markovitz David M
University of Michigan Medical Center, 5220 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5640, USA.
J Virol. 2008 Oct;82(19):9329-36. doi: 10.1128/JVI.00646-08. Epub 2008 Jul 16.
Actively replicating endogenous retroviruses entered the human genome millions of years ago and became a stable part of the inherited genetic material. They subsequently acquired multiple mutations, leading to the assumption that these viruses no longer replicate. However, certain human tumor cell lines have been shown to release endogenous retroviral particles. Here we show that RNA from human endogenous retrovirus K (HERV-K) (HML-2), a relatively recent entrant into the human genome, can be found in very high titers in the plasma of patients with lymphomas and breast cancer as measured by either reverse transcriptase PCR or nucleic acid sequence-based amplification. Further, these titers drop dramatically with cancer treatment. We also demonstrate the presence of reverse transcriptase and viral RNA in plasma fractions that contain both immature and correctly processed HERV-K (HML-2) Gag and envelope proteins. Finally, using immunoelectron microscopy, we show the presence of HERV-K (HML-2) virus-like particles in the plasma of lymphoma patients. Taken together, these findings demonstrate that elements of the endogenous retrovirus HERV-K (HML-2) can be found in the blood of modern-day humans with certain cancers.
数百万年前，活跃复制的内源性逆转录病毒进入人类基因组，并成为遗传物质的稳定组成部分。它们随后发生了多次突变，导致人们认为这些病毒不再复制。然而，某些人类肿瘤细胞系已被证明会释放内源性逆转录病毒颗粒。在此我们表明，通过逆转录酶聚合酶链反应或基于核酸序列的扩增检测发现，人类内源性逆转录病毒K（HERV-K）（HML-2）（一种相对较新进入人类基因组的病毒）的RNA在淋巴瘤和乳腺癌患者血浆中的滴度非常高。此外，随着癌症治疗，这些滴度会急剧下降。我们还在含有未成熟和正确加工的HERV-K（HML-2）Gag和包膜蛋白的血浆组分中证实了逆转录酶和病毒RNA的存在。最后，利用免疫电子显微镜，我们在淋巴瘤患者血浆中发现了HERV-K（HML-2）病毒样颗粒。综上所述，这些发现表明内源性逆转录病毒HERV-K（HML-2）的成分可在患有某些癌症的现代人类血液中被发现。
