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@ARTICLE{Eilebrecht:132549,
      author       = {S. Eilebrecht$^*$ and A. Hotz-Wagenblatt$^*$ and V.
                      Sarachaga$^*$ and A. Burk$^*$ and K. Falida$^*$ and D.
                      Chakraborty$^*$ and E. Nikitina$^*$ and C. Tessmer$^*$ and
                      C. Whitley$^*$ and C. Sauerland$^*$ and K. Gunst$^*$ and I.
                      Grewe$^*$ and T. Bund$^*$},
      title        = {{E}xpression and replication of virus-like circular {DNA}
                      in human cells.},
      journal      = {Scientific reports},
      volume       = {8},
      number       = {1},
      issn         = {2045-2322},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {DKFZ-2018-00227},
      pages        = {2851},
      year         = {2018},
      abstract     = {The consumption of bovine milk and meat is considered a
                      risk factor for colon- and breast cancer formation, and milk
                      consumption has also been implicated in an increased risk
                      for developing Multiple Sclerosis (MS). A number of highly
                      related virus-like DNAs have been recently isolated from
                      bovine milk and sera and from a brain sample of a MS
                      patient. As a genetic activity of these
                      Acinetobacter-related bovine milk and meat factors (BMMFs)
                      is unknown in eukaryotes, we analyzed their expression and
                      replication potential in human HEK293TT cells. While all
                      analyzed BMMFs show transcriptional activity, the MS brain
                      isolate MSBI1.176, sharing homology with a transmissible
                      spongiform encephalopathy-associated DNA molecule, is
                      transcribed at highest levels. We show expression of a
                      replication-associated protein (Rep), which is highly
                      conserved among all BMMFs, and serological tests indicate a
                      human anti-Rep immune response. While the cow milk isolate
                      CMI1.252 is replication-competent in HEK293TT cells,
                      replication of MSBI1.176 is complemented by CMI1.252,
                      pointing at an interplay during the establishment of
                      persistence in human cells. Transcriptome profiling upon
                      BMMF expression identified host cellular gene expression
                      changes related to cell cycle progression and cell viability
                      control, indicating potential pathways for a pathogenic
                      involvement of BMMFs.},
      cin          = {F200 / W180 / W170},
      ddc          = {000},
      cid          = {I:(DE-He78)F200-20160331 / I:(DE-He78)W180-20160331 /
                      I:(DE-He78)W170-20160331},
      pnm          = {316 - Infections and cancer (POF3-316)},
      pid          = {G:(DE-HGF)POF3-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29434270},
      pmc          = {pmc:PMC5809378},
      doi          = {10.1038/s41598-018-21317-w},
      url          = {https://inrepo02.dkfz.de/record/132549},
}