Efficient mobilization of E1-deleted adenovirus type 5 vectors by wild-type adenoviruses of other serotypes.
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 DeltaE1DeltaE3-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 DeltaE1-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.
Rademaker
Hendrik J
HJ
Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands1.
El Hassan
Mohamed A Abou
MAA
Department of Medical Oncology, Free University Medical Center, Amsterdam, The Netherlands2.|Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands1.
Versteeg
Gijs A
GA
Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands1.
Rabelink
Martijn J W E
MJWE
Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands1.
Hoeben
Rob C
RC
Department of Molecular Cell Biology, Leiden University Medical Center, Wassenaarseweg 72, 2333 AL Leiden, The Netherlands1.
D017498:Adenovirus E1 Proteins / Q000172:deficiency / Q000235:genetics*; D000260:Adenoviruses, Human / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D017353:Gene Deletion; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D012703:Serotyping; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D017498:Adenovirus E1 Proteins