The nucleotide sequences of the haemagglutinin esterase (HE) genes of
18 influenza C virus strains isolated in Japan during the period from
1964 to 1988 (11 published and 7 new sequences) were analysed to exami
ne their evolutionary relationships. The phylogenetic tree constructed
by the maximum parsimony method revealed the existence of four discre
te lineages (I to IV), one of which (lineage III) may have died out in
the late 1970s. Sequential evolution was demonstrated within seven st
rains of lineage I, which allowed estimation of an evolutionary rate o
f 0.49 x 10(-3) nucleotide substitutions per site per year, a value co
rresponding to about one-ninth of the rates of human influenza A virus
haemagglutinin genes. In the previously proposed immunodominant regio
n on HE protein (positions 178 to 217), there was little or no amino a
cid sequence divergence among viruses on the same lineage although con
siderable divergence was seen among those on different lineages, raisi
ng the possibility that immune selection may not have played a signifi
cant role in the evolution of the glycoprotein, at least not after sep
aration into lineages occurred. It was also found that the HE genes of
the seven isolates obtained outside Japan during 1966-1983 could be e
ach assigned to one of lineages I, II and IV, which suggests that infl
uenza C virus is capable of spreading worldwide.