QUANTITATIVE-ANALYSIS OF GENOMIC POLYMORPHISM OF HERPES-SIMPLEX VIRUSTYPE-1 STRAINS FROM 6 COUNTRIES - STUDIES OF MOLECULAR EVOLUTION AND MOLECULAR EPIDEMIOLOGY OF THE VIRUS

Using the presence or absence of 63 variable restriction endonuclease (RE) sites selected from 225 sites with six REs, genomic polymorphism of 242 herpes simplex virus type 1 (HSV-1) strains from six countries (Japan, Korea, China, Sweden, U.S.A. and Kenya) was quantitatively ana lysed. Twenty-five of the 63 sites were found to differ between Korean and Kenyan strains. In contrast, only three and six sites were found to differ between isolates from Sweden and the U.S.A. and between thos e from Korea and China, respectively, suggesting that they are closely related to each other. In this way, characterization of 63 sites enab led us to categorize 186 distinct HSV-1 genotypes from 242 individuals . Some strains from Japan, Korea and China shared the same genotypes, indicating that they are phylogenetically closely related. Many signif icant correlation coefficients ( \ r \ > 0.42; P < 0.01) between pairs of sites were found in isolates from the three Asian countries (Japan , Korea and China) as well as in those from Sweden and the U.S.A., sug gesting that HSV-1 strains from within the same ethnic groups are evol utionarily closer. The average number of nucleotide substitutions per nucleotide, as defined by nucleotide diversity (pi), was estimated for HSV-1 genomes within (pi(X) or pi(Y)) and between (pi(XY)) countries. On the basis of 225 sites, nucleotide diversity for Kenyan isolates w as 0.0056, almost three times higher than that for Korean isolates, im plying that Kenyan HSV-1 genomes are much more diverse than those from Korea. In addition, the diversity between HSV-1 isolates from differe nt countries (pi(XY)) was highest between isolates from the three Asia n countries and Kenya (0.0075 to 0.0081) and lowest among those from t he three Asian countries (0.0032 to 0.0040). The mutation rate (lambda ) for HSV-1 was estimated to be 3.5 x 10(-8)/site/year. Ah these findi ngs show that the evolution of HSV-1 may be host-dependent and very sl ow.