Human endogenous retrovirus K (HML-2) elements in the plasma of people with lymphoma and breast cancer

被引:162
作者
Contreras-Galindo, Rafael [1 ]
Kaplan, Mark H. [1 ]
Leissner, Philippe [5 ,6 ]
Verjat, Thibault [5 ,6 ]
Ferlenghi, Ilaria [7 ]
Bagnoli, Fabio [7 ]
Giusti, Fabiola [8 ]
Dosik, Michael H. [9 ]
Hayes, Daniel F. [2 ,3 ,4 ]
Gitlin, Scott D. [2 ,10 ]
Markovitz, David M. [1 ]
机构
[1] Univ Michigan, Med Ctr, Div Infect Dis, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Med Ctr, Div Hematol Oncol, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Med Ctr, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[5] BioMerieux SA, Dept Oncol, F-38024 Grenoble, France
[6] BioMerieux SA, Dept Human Genet, F-38024 Grenoble, France
[7] Novartis Vaccines & Diagnost, Dept Cellular Microbiol & Informat, F-38024 Grenoble, France
[8] Univ Siena, Dept Evolutionary Biol, I-53100 Siena, Italy
[9] N Shore Hematol Oncol Associates, Setauket, NY 11733 USA
[10] Vet Affairs Hlth Syst, Dept Internal Med, Div Hematol Oncol, Ann Arbor, MI 48104 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1128/JVI.00646-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:9329 / 9336
页数:8
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