Methods for enhancing the production of viral vaccines in animal cell
culture are described. These methods rely on the manipulation of the
cellular levels of certain interferon induced antiviral activities, in
particular, cellular levels of double-stranded RNA (dsRNA) dependent
kinase (PKR) and 2'-5' oligoadenylate synthetase (2-5A synthetase). In
cell cultures deficient for PKR or 2-5A synthetase, viral yield is
enhanced by several orders of magnitude over cell cultures with normal
levels of these proteins making these cell cultures useful for the
production of viral vaccines.