Expression patterns of transcribed human endogenous retrovirus HERV-K(HML-2) loci in human tissues and the need for a HERV Transcriptome Project

• Published in: BMC genomics Vol. 9; no. 1; p. 354
• Main Authors: Flockerzi, Aline, Ruggieri, Alessia, Frank, Oliver, Sauter, Marlies, Maldener, Esther, Kopper, Bernd, Wullich, Bernd, Seifarth, Wolfgang, Müller-Lantzsch, Nikolaus, Leib-Mösch, Christine, Meese, Eckart, Mayer, Jens
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.07.2008; BioMed Central; BMC
• Subjects: Base Sequence; Brain - cytology; Brain - metabolism; Brain - pathology; Breast - cytology; Breast - metabolism; Breast - pathology; Cell Line, Tumor; DNA, Complementary - genetics; Endogenous Retroviruses - genetics; Endogenous Retroviruses - metabolism; Expressed Sequence Tags; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genetic aspects; Genetic transcription; Genome, Human; Humans; Neoplasms, Germ Cell and Embryonal - genetics; Physiological aspects; Proviruses - genetics; Proviruses - metabolism; Retroviruses; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Germany
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/1471-2164-9-354

A significant proportion of the human genome is comprised of human endogenous retroviruses (HERVs). HERV transcripts are found in every human tissue. Expression of proviruses of the HERV-K(HML-2) family has been associated with development of human tumors, in particular germ cell tumors (GCT). Very little is known about transcriptional activity of individual HML-2 loci in human tissues, though. By employing private nucleotide differences between loci, we assigned approximately 1500 HML-2 cDNAs to individual HML-2 loci, identifying, in total, 23 transcriptionally active HML-2 proviruses. Several loci are active in various human tissue types. Transcription levels of some HML-2 loci appear higher than those of other loci. Several HML-2 Rec-encoding loci are expressed in GCT and non-GCT tissues. A provirus on chromosome 22q11.21 appears strongly upregulated in pathologic GCT tissues and may explain high HML-2 Gag protein levels in GCTs. Presence of Gag and Env antibodies in GCT patients is not correlated with activation of individual loci. HML-2 proviruses previously reported capable of forming an infectious HML-2 variant are transcriptionally active in germ cell tissue. Our study furthermore shows that Expressed Sequence Tag (EST) data are insufficient to describe transcriptional activity of HML-2 and other HERV loci in tissues of interest. Our, to date, largest-scale study reveals in greater detail expression patterns of individual HML-2 loci in human tissues of clinical interest. Moreover, large-scale, specialized studies are indicated to better comprehend transcriptional activity and regulation of HERVs. We thus emphasize the need for a specialized HERV Transcriptome Project.