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Journal of General Virology (2002), 83, 1311-1314.
© 2002 Society for General Microbiology

Animal: DNA Viruses

Efficient mobilization of E1-deleted adenovirus type 5 vectors by wild-type adenoviruses of other serotypes

Hendrik J. Rademaker1, Mohamed A. Abou El Hassan1,2, Gijs A. Versteeg1, Martijn J. W. E. Rabelink1 and Rob C. Hoeben1

Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands1
Department of Medical Oncology, Free University Medical Center, Amsterdam, The Netherlands2

Author for correspondence: Rob Hoeben. Fax +31 71 527 6284. e-mail R.C.Hoeben{at}lumc.nl

Mobilization of replication-deficient adenovirus vectors can lead to spread and shedding of the vector. Here we show that in cultured HepG2 cells wild-type (wt) adenoviruses of subgroup A (Ad12), B (Ad7, 11 and 16), C (Ad1, 2 and 5) and E (Ad4) can efficiently mobilize Ad5CMVluc, a {Delta}E1{Delta}E3-Ad5 vector carrying the firefly luciferase gene as reporter. In addition, we show that Ad5CMVluc can be propagated on Ad12E1-transformed human embryonic retinoblasts. This provides evidence that expression of the E1 region of Ad12 is sufficient for mobilizing {Delta}E1-Ad5-derived vectors. Thus, in therapeutic applications of replication-defective Ad vectors any active Ad infection is of potential concern, independent of the serotype involved. To prevent vector mobilization by wt Ads, new vectors should be developed in which essential functions such as the initiation of DNA replication and genome packaging are restricted.




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