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Journal of Virology, October 2008, p. 10008-10016, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01016-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Endogenous Retrovirus Family HERV-K(HML-2) RNA Transcripts Are Selectively Packaged into Retroviral Particles Produced by the Human Germ Cell Tumor Line Tera-1 and Originate Mainly from a Provirus on Chromosome 22q11.21{triangledown} ,{dagger}

Klemens Ruprecht,1* Humberto Ferreira,1 Aline Flockerzi,2,{ddagger} Silke Wahl,1 Marlies Sauter,1 Jens Mayer,2 and Nikolaus Mueller-Lantzsch1

Institut für Virologie und,1 Institut für Humangenetik, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany2

Received 15 May 2008/ Accepted 25 July 2008

The human germ cell tumor line Tera-1 produces retroviral particles which are encoded by the human endogenous retrovirus family HERV-K(HML-2). We show here, by quantitative reverse transcriptase PCR, that HML-2 gag and env RNA transcripts are selectively packaged into Tera-1 retroviral particles, whereas RNAs from cellular housekeeping genes and from other HERV families (HERV-H and HERV-W) are nonselectively copackaged. Assignment of cloned HML-2 gag and env cDNAs from Tera-1 retroviral particles to individual HML-2 loci in the human genome demonstrated that HML-2 RNA transcripts packaged into Tera-1 retroviral particles originate almost exclusively from an HML-2 provirus on chromosome 22q11.21. Based on relative cloning frequencies, this provirus was the most active among a total of eight transcribed HML-2 loci identified in Tera-1 cells. These data suggest that at least one HML-2 element, that is, the HML-2 provirus on 22q11.21, has retained the capacity for packaging RNA into HML-2-encoded retroviral particles. Given its elevated transcriptional activity and the presence of a full-length Gag open reading frame, the 22q11.21 HML-2 provirus may also significantly contribute to Gag protein and thus particle production in Tera-1 cells. Our findings provide important clues to the generation and biological properties of HML-2-encoded particles. In addition, copackaging of non-HML-2 HERV transcripts in HML-2-encoded particles should inform the debate about endogenous retroviral particles putatively encoded by non-HML-2 HERV families that have previously been described for other human diseases, such as multiple sclerosis.

* Corresponding author. Mailing address: Institut für Virologie, Universitätsklinikum des Saarlandes, Haus 47, 66421 Homburg/Saar, Germany. Phone: 49 (0)6841 16 23931. Fax: 49 (0)6841 16 23980. E-mail: klemens.ruprecht{at}uniklinikum-saarland.de

{triangledown} Published ahead of print on 6 August 2008.

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

{ddagger} Present address: Institut für Molekulare Zellbiologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.

Journal of Virology, October 2008, p. 10008-10016, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.01016-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Heslin, D. J., Murcia, P., Arnaud, F., Van Doorslaer, K., Palmarini, M., Lenz, J. (2009). A Single Amino Acid Substitution in a Segment of the CA Protein within Gag That Has Similarity to Human Immunodeficiency Virus Type 1 Blocks Infectivity of a Human Endogenous Retrovirus K Provirus in the Human Genome. J. Virol. 83: 1105-1114 [Abstract] [Full Text]  


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