Epidemiology of influenza C virus in man: multiple evolutionary lineages and low rate of change

The nucleotide sequences of nonstructural protein (NS) genes of human influenza C viruses isolated between 1947 and 1983 were determined and compared. Assuming constant evolutionary rates, the extent of nucleotide differences among NS genes does not correspond to the isolation years of the strains. This suggests that more than one gene lineage is present in the population. Furthermore, examination of the eight C virus NS gene sequences by the maximum parsimony method (W. M. Fitch, 1971, Syst. Zool. 20, 406-416) yielded phylogenetic trees that were grossly different from those obtained using the hemagglutinin genes for the same eight isolates. This result is compatible with the idea of reassortment of genes in nature across lineages of influenza C viruses. The sequence analysis also suggests that nucleotide substitutions occur at a lower rate in the C virus NS genes than in influenza A virus NS genes.