Molecular biological basis of measles virus strain differences

Summary

Biological differences between measles strains have been described in relation to plaque type, fusiogenicity, haemagglutination, neurovirulence in animal models, temperature-sensitivity, cold adaptation, ability to induce interferon, presence of defective interfering particles as well as, most importantly, attenuation in human infection. The molecular (nucleotide sequence) basis of few, if any, of these changes has been elucidated. Recently described differences in monoclonal antibody (Mcab) binding properties of the nucleocapsid proteins of different strains have been linked to sequence variation in B cell epitopes. Similarly, B cell epitopes in the haemagglutinin have now been defined by sequencing Mcab escape mutants. These appear to be localized in a region of moderate strain variability. We have also identified a mutation linked to the salt dependency for haemagglutination of some strains. A large number of mutations have been described for viruses isolated from SSPE and other persistent infections. Mutations in the M gene (biased hypermutation and premature stop codons) and in the F gene (truncation of cytoplasmic tails) have been reviewed and their significance in SSPE is discussed. The recent discovery of a number of different lineages of MV has indicated co-circulation and global distribution of some strains. All vaccines belong to one lineage. The other virus strains are classified into various lineages. Differences in glycosylation sites have been observed and these may be of biological importance. However, it is as yet unknown whether the different lineages have biological significance beyond escape from immunological pressure.