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Journal of Virology, September 2007, p. 9346-9356, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00781-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

In Vivo and In Vitro Intragenomic Rearrangement of TT Viruses{triangledown}

Ludmila Leppik,1 Karin Gunst,1 Matti Lehtinen,2 Joakim Dillner,3 Karin Streker,1 and Ethel-Michele de Villiers1*

Division for the Characterization of Tumor Viruses, Deutsches Krebsforschungszentrum, Heidelberg, Germany,1 Department of Infectious Disease Epidemiology, National Public Health Institute, Helsinki, Finland,2 Department of Medical Microbiology, Lund University, Malmö, Sweden3

Received 11 April 2007/ Accepted 14 June 2007

The in vitro replication of the Torque teno virus (TT virus) tth8 full-length genome and particle formation in a Hodgkin's lymphoma-derived cell line after transfection with cloned viral DNA were demonstrated. Analyses of the transcription patterns of tth8 and tth7 TT virus isolates in a number of lymphoma and T-cell leukemia cell lines indicated differential additional splicing events and intragenomic rearrangement generating open reading frames which could not be deducted from the genomic sequence. We also demonstrated the presence of rearranged TT virus genomes in vivo in sera taken from pregnant mothers whose children later developed childhood leukemia, as well as sera from control mothers. Control experiments using religated cloned genomic tth8 DNA mixed with cellular DNA did not result in such subviral molecules. These subviral isolates ranged from 172 bp to full-length TT virus genomes. Possible in vivo selection for specific rearranged molecules was indicated by the presence of one isolate (561 bp) in 11 serum samples. It remains to be clarified whether selected rearranged subviral components resulting from specific TT virus types may contribute to the initiation of disease. These data demonstrate new features of TT viruses suggesting possible similarities to plant viruses of the family Geminiviridae, as well as raise questions about the documented plurality and diversity of anelloviruses.

* Corresponding author. Mailing address: Division for the Characterization of Tumor Viruses, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany. Phone: 49-6221-424655. Fax: 49-6221-424822. E-mail: e.devilliers{at}dkfz.de

{triangledown} Published ahead of print on 27 June 2007.

Journal of Virology, September 2007, p. 9346-9356, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00781-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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