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Comprehensive Analysis of Human Endogenous Retrovirus Transcriptional Activity in Human Tissues with a Retrovirus-Specific Microarray

Wolfgang Seifarth,^1*, Oliver Frank,^1, Udo Zeilfelder,¹ Birgit Spiess,¹ Alex D. Greenwood,^2,3 Rüdiger Hehlmann,¹ and Christine Leib-Mösch^1,2

Medical Clinic III, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim,¹ GSF-National Research Center for Environment and Health, Institute of Molecular Virology, Neuherberg,² Technical University of Munich, Institute of Virology, Munich,Germany³

Received 5 May 2004/ Accepted 19 August 2004

Retrovirus-like sequences account for 8 to 9% of the human genome. Among these sequences, about 8,000 pol-containing proviral elements have been identified to date. As part of our ongoing search for active and possibly disease-relevant human endogenous retroviruses (HERVs), we have recently developed an oligonucleotide-based microarray. The assay allows for both the detection and the identification of most known retroviral reverse transcriptase (RT)-related nucleic acids in biological samples. In the present study, we have investigated the transcriptional activity of representative members of 20 HERV families in 19 different normal human tissues. Qualitative evaluation of chip hybridization signals and quantitative analysis by real-time RT-PCR revealed distinct HERV activity in the human tissues under investigation, suggesting that HERV elements are active in human cells in a tissue-specific manner. Most active members of HERV families were found in mRNA prepared from skin, thyroid gland, placenta, and tissues of reproductive organs. In contrast, only few active HERVs were detectable in muscle cells. Human tissues that lack HERV transcription could not be found, confirming that human endogenous retroviruses are permanent components of the human transcriptome. Distinct activity patterns may reflect the characteristics of the regulatory machinery in these cells, e.g., cell type-dependent occurrence of transcriptional regulatory factors.

W.S. and O.F. contributed equally.

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