CONSISTENT SELECTION OF MUTATIONS IN THE 5'-UNTRANSLATED REGION OF ORAL POLIOVIRUS VACCINE UPON PASSAGING IN-VITRO

We have previously found that upon passaging type 3 oral poliovirus va ccine (OPV) in cell cultures the proportion of revertants at nucleotid e 472 rapidly increases [Chumakov et al.: Proceedings of the National Academy of Sciences of the United States of America 88:199-203 1991]. Systematic study on the accumulation of these revertants showed that i t was dependent on the multiplicity of infection and the temperature a t which virus was grown. Revertants at position 472 of type 3 OPV accu mulated faster in vaccines derived from Sabin Original (SO) substrain than from RNA-plaque purified (RSO) substrain. The rate of accumulatio n of 472-C revertants differed among cell lines and was higher in over grown cell cultures suggesting that host factors are involved in the s election of mutants. We also found that accumulation of mutants occurr ed in vitro at position 480 in type 1 and position 481 in type 2 OPV, making the selection for revertants in domain F of the 5'-noncoding re gion a general phenomenon for all three Sabin strains. Assessment of t he abundance of these mutants may be used for evaluation of the qualit y of OPV lots.