Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer
Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer
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DOI：
10.1128/jvi.00646-08
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发表时间：
2008-10-01
影响因子：
5.4
通讯作者：
Markovitz, David M.
中科院分区：
文献类型：
--
作者：
Contreras-Galindo, Rafael;Kaplan, Mark H.;Markovitz, David M.
活跃复制的内源性逆转录病毒在数百万年前进入人类基因组，并成为遗传性遗传物质的稳定部分。随后，它们获得了多种突变，导致人们假设这些病毒不再复制。然而，某些人类肿瘤细胞系已被证明可以释放内源性逆转录病毒颗粒。在这里，我们表明，通过逆转录酶 PCR 或基于核酸序列的扩增测量，可以在淋巴瘤和乳腺癌患者的血浆中以非常高的滴度发现人内源性逆转录病毒 K (HERV-K) (HML-2) 的 RNA，这是人类基因组中相对较新的进入者。此外，随着癌症治疗，这些滴度急剧下降。我们还证明了血浆组分中存在逆转录酶和病毒 RNA，其中含有未成熟且正确加工的 HERV-K (HML-2) Gag 和包膜蛋白。最后，使用免疫电子显微镜，我们显示淋巴瘤患者血浆中存在 HERV-K (HML-2) 病毒样颗粒。总而言之，这些发现表明，内源性逆转录病毒 HERV-K (HML-2) 的成分可以在患有某些癌症的现代人类的血液中找到。
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.