Genomic heterogeneity maps to tandem repeat sequences in the herpes simplex virus type 2 UL region

Two BamHI Y and W fragments in the unique long sequence (UL) of the herpes simplex virus type 2 (HSV-2) were found to be heterogeneous in size among clones derived from a single strain as well as from epidemiologically unrelated isolates. More detailed restriction maps of these BamHI fragments were constructed and the heterogeneous subfragments were defined, cloned, and sequenced in order to investigate the mechanism causing the size difference. The subfragment of BamHI Y contained a tandem repeat sequence consisting of different numbers of 15 bp, 5′AGGGGCGGCTGGGGC3′ as one unit among three isolates, and the subfragment of BamHI W contained the other tandem repeat sequence, 9 bp, 5′CCTCCCGCC3′. In the UL of the HSV-2 strain, these tandem repeat sequences were conserved and each repeat number appeared to be highly variable through viral genome replication. These results showed that the fragment length polymorphisms in these regions were attributable to the variation of unit numbers of the tandem repeat sequences.