The distribution of restriction endonuclease (RE) sites was compared for 84 herpes simplex virus type 1 (HSV-1) isolates obtained from the ganglia, facial lesions, genital lesions and from brain tissue from herpes encephalitis cases. The isolates came from Canada, the U.K., the U.S.A. and Japan. Out of a total of 224 sites identified, 87 were variable. Three of the 30 most variable sites were at significantly ( < 0.05) different frequencies in groups of isolates from distinct anatomical sites of isolation; one of these, and a further two sites, were at significantly different frequencies in groups from distinct geographical origins. There are at least two inter-related linkage groups. However, most of the site combinations appear to be random. The variability of RE sites in contiguous genome segments, which include both non-coding and coding sequences, show a marked heterogeneity, indicating that some viral gene sequences are more variable than others. The three RE sites at different frequencies in viral groups from distinct anatomical sites of isolation are in two genome segments: map units 27 to 35 and 50 to 57. We infer from the observed associations with anatomical site of viral isolation that part of at least one of these segments may modulate viral virulence in man following infection.


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