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Journal of Virology, February 2008, p. 1360-1367, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.02098-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mouse Mammary Tumor Virus Integration Site Selection in Human and Mouse Genomes ^,

Research Institute for Virology and Biomedicine, University of Veterinary Medicine Vienna, Vienna A-1210, Austria,¹ Christian-Doppler Laboratory for Gene Therapeutic Vector Development, Vienna A-1210, Austria,² Austrianova Biotechnology GmbH, Vienna A-1210, Austria,³ Emergentec Biodevelopment GmbH, Vienna A-1010, Austria⁴

Received 21 September 2007/ Accepted 5 November 2007

Based on integration site preferences, retroviruses can be placed into three groups. Viruses that comprise the first group, murine leukemia virus and foamy virus, integrate preferentially near transcription start sites. The second group, notably human immunodeficiency virus and simian immunodeficiency virus, preferentially targets transcription units. Avian sarcoma-leukosis virus (ASLV) and human T-cell leukemia virus (HTLV), forming the third group, show little preference for any genomic feature. We have previously shown that some human cells sustain mouse mammary tumor virus (MMTV) infection; therefore, we infected a susceptible human breast cell line, Hs578T, and, without introducing a species-specific bias, compared the MMTV integration profile to those of other retroviruses. Additionally, we infected a mouse cell line, NMuMG, and thus we could compare MMTV integration site selection in human and mouse cells. In total, we examined 468 unique MMTV integration sites. Irrespective of whether human or mouse cells were infected, no integration bias favoring transcription start sites was detected, a profile that is reminiscent of that of ASLV and HTLV. However, in contrast to ASLV and HTLV, not even a modest tendency in favor of integration within genes was observed. Similarly, repetitive sequences and genes that are frequently tagged by MMTV in mammary tumors were not preferentially targeted in cell culture either in mouse or in human cells; hence, we conclude that MMTV displays the most random dispersion of integration sites among retroviruses determined so far.

Published ahead of print on 21 November 2007.

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

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