The adenovirus E1A and E1B19K genes provide a helper function for transfection-based adeno-associated virus vector production

Although the adenoviral Ell, E2A, E4 and VA RNA regions are required for efficient adeno-associated virus (AAV) vector production, the role that the individual Ell genes (E1A, E1B19K, E1B55K and protein IX) play in AAV vector production has not been clearly determined. Ell mutants were analysed for their ability to mediate AAV vector production in HeLa or KB cells, when cotransfected with plasmids encoding all other packaging functions. Disruption of E1A and E1B19K genes resulted in vector yield reduction by up to 10- and 1 00-fold, respectively, relative to the wild-type Ell. Interruption of the E1B55K and protein IX genes had a modest effect on vector production. Interestingly, expression of anti-apoptotic E1B19K cellular homologues such as BcI-2 or Bcl-X-L fully complemented E1B19K mutants for AAV vector production. These findings may be valuable for the future development of packaging cell lines for AAV vector production.