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Journal of Virology, October 2008, p. 9329-9336, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00646-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Endogenous Retrovirus K (HML-2) Elements in the Plasma of People with Lymphoma and Breast Cancer {triangledown} ,{dagger}

Rafael Contreras-Galindo,1,{ddagger} Mark H. Kaplan,1,{ddagger} Philippe Leissner,4 Thibault Verjat,4 Ilaria Ferlenghi,5 Fabio Bagnoli,5 Fabiola Giusti,6 Michael H. Dosik,7 Daniel F. Hayes,2,3 Scott D. Gitlin,2,8 and David M. Markovitz1*

Divisions of Infectious Diseases,1 Hematology/Oncology, Department of Internal Medicine,2 Breast Oncology Program, Comprehensive Cancer Center, University of Michigan Medical Center, Ann Arbor, Michigan 48109,3 Departments of Oncology and Human Genetics, BioMérieux SA, Grenoble 38024, France,4 Department of Cellular Microbiology and Informatics, Novartis Vaccines & Diagnostics, Siena 53100, Italy,5 Department of Evolutionary Biology, University of Siena, Siena 53100, Italy,6 North Shore Hematology/Oncology Associates, Setauket, New York 11733,7 Division of Hematology/Oncology, Department of Internal Medicine, Veterans Affairs Health System, Ann Arbor, Michigan 481048

Received 21 March 2008/ Accepted 9 July 2008

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.

* Corresponding author. Mailing address: University of Michigan Medical Center, 5220 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5640. Phone: (734) 647-1786. Fax: (734) 764-0101. E-mail: dmarkov{at}umich.edu

{triangledown} Published ahead of print on 16 July 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} These authors contributed equally.

Journal of Virology, October 2008, p. 9329-9336, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00646-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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