The Temperature Sensitivity of the Sabin Type 3 Vaccine Strain of Poliovirus: Molecular and Structural Effects of a Mutation in the Capsid Protein VP3

1 NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG 2 MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR 3 Department of Microbiology, University of Reading, London Road, Reading RG1 5AQ, U.K. and 4 Scripps Institute, 10666 North Torrey Pines Road, La Jolla, California 92037, U.S.A. The growth of the Sabin strain of type 3 poliovirus is reduced at high temperatures compared to that of its virulent precursor strain Leon. Recombinant viruses have been generated from infectious cDNA clones and demonstrate that the temperature-sensitive (ts) phenotype is mainly attributable to a difference in residue 91 of the virion protein VP3. Examination of non-ts mutants derived in vitro or in vivo reveals the existence of second site mutations some of which are clearly able to suppress the ts phenotype. The location of residue 91 of VP3, and of a number of candidate suppressor mutations, in the atomic structure of the virion suggests that the ts phenotype may result in destabilization of the particle and that the suppressors may function by stabilizing specific interfaces. It is not yet clear whether the ts phenotype is expressed at the level of the particle or in the form of defects in assembly or uncoating of the virion, or all three. Keywords: poliovirus, capsid protein, temperature-sensitive mutants Received 2 November 1988; accepted 13 January 1989.