SEQUENCE DIVERGENCE OF MEASLES-VIRUS HEMAGGLUTININ DURING NATURAL EVOLUTION AND ADAPTATION TO CELL-CULTURE

Phylogenetic analysis of the sequence of the H gene of 75 measles viru s (MV) strains (32 published and 43 new sequences) was carried out. Th e lineage groups described from comparison of the nucleotide sequences encoding the C-terminal regions of the N protein of MV were the same as those derived from the H gene sequences in almost all cases. The da tabases document a number of distinct genotype switches that have occu rred in Madrid (Spain). Well-documented is the complete replacement of lineage group C2, the common European genotype at that time, with tha t of group D3 around the autumn of 1993. No further isolations of grou p C2 took place in Madrid after this time. The rate of mutation of the H gene sequences of MV genotype D3 circulating in Madrid from 1993 to 1996 was very low (5 x 10(-4) per annum for a given nucleotide positi on). This is an order of magnitude lower than the rates of mutation ob served in the HN genes of human influenza A viruses. The ratio of expr essed over silent mutations indicated that the divergence was not driv en by immune selection in this gene. Variations in amino acid 117 of t he H protein (F or L) may be related to the ability of some strains to haemagglutinate only in the presence of salt. Adaptation of MV to dif ferent primate cell types was associated with very small numbers of mu tations in the H gene. The changes could not be predicted when virus p reviously grown in human B cell lines was adapted to monkey Vero cells . In contrast, rodent brain-adapted viruses displayed a lot of amino a cid sequence variation from normal MV strains. There was no convincing evidence for recombination between MV genotypes.