AN ESTIMATION OF THE NUCLEOTIDE SUBSTITUTION RATE AT DEFINED POSITIONS IN THE INFLUENZA-VIRUS HEMAGGLUTININ GENE

The mutation rates to a viable mar (monoclonal antibody-resistant muta nt) genotype of wild-type influenza (A/Victoria/3/75; H3N2) virus or i ts mutator variant strains have been previously determined. In order t o estimate the mutation rates per nucleotide position, the sequence al terations present in 44 mar mutants isolated from either the wild-type or the mut43 mutator strain have been determined. These mar mutants w ere selected with either of two non-overlapping, haemagglutinin-specif ic, monoclonal antibodies (2G10 and p7). Most of the protein changes w ere identified as substitutions of large, charged amino acids for glyc ine residues, as the result of G to A transitions. Particularly intere sting amino acid changes, not previously reported, were observed in th e p7 monoclonal antibody-specific mutants, in which only Gly to Ser an d Gly to Asp at position 226 were detected. The identification of the nucleotide substitutions responsible for the mar phenotype has allowed the calculation of approximate values for the total mutation rates at these positions.